PHA soft capsule as well as preparation method and application thereof

Abstract

The invention relates to the technical field of soft capsules, in particular to a PHA soft capsule and a preparation method and application thereof. The PHA soft capsule comprises a capsule shell, wherein the capsule shell is mainly composed of PHA and nano-micron cellulose; the PHA is selected from one or more of P34HB3HV, P34HB5HV, P34HB, PHBV and PHBHHx, and the PHA is selected from one or more of P34HB5HV, P34HB, PHBHV and PHBHHx. Additives such as alum do not need to be added, the degradation product trihydroxybutyric acid of the main component PHA of the capsule shell is beneficial to the human body, the selected PHA is better in film forming property, can increase the temperature resistance, does not need refrigeration preservation, does not have the problems that the capsule shell is too hard and too crisp, and does not have the oil leakage phenomenon caused by softening or breaking of the capsule shell; and the method has the advantages of simple production process, short forming period, low processing temperature, low energy consumption and the like, and has a wide application prospect.

Description

Technical Field

[0001] The invention relates to the technical field of soft capsules, and in particular to a PHA soft capsule and a preparation method and application thereof. Background Art

[0002] Soft capsules have been widely used in the fields of medicine and health food. According to the raw materials, the commonly used soft capsules are mainly divided into animal gelatin soft capsules and plant soft capsules.

[0003] Animal gelatin is mainly extracted from animals, and then boiled with additives such as alum. However, gelatin soft capsules have certain defects, such as low temperature resistance, easy to soften, melt, and stick when the temperature is higher than 35°C, and eventually lead to oil leakage, and generally need to be refrigerated. And it adds additives such as alum that are harmful to the human body. Plant soft capsules solve the problem of low temperature resistance, can withstand higher temperatures, and are easier to store. However, plant soft capsules also have some disadvantages, such as: plant soft capsules do not solve the problem of long cycle in the molding process, because the capsule components are all water-absorbing substances, and need to be treated with gelatin first, the gelatinization time (such as carrageenan) is long, and after gelatinization, it needs to be kept warm, and the time for drying into capsules is very long, usually higher than 20min, or even more than ten hours, which consumes time and energy. The inventor studied the preparation of soft capsules from biodegradable materials and found that the existing schemes have problems such as hard and brittle capsule shells, easy to crack, low rubber seam rate, and high processing temperature, which cannot be actually applied to soft capsules. Therefore, it is urgent to provide a new type of biodegradable soft capsule and its preparation method. Summary of the invention

[0004] In order to solve the above technical problems, the present invention provides a PHA soft capsule and a preparation method and use thereof.

[0005] In a first aspect, the present invention provides a PHA soft capsule, wherein the PHA soft capsule comprises a capsule shell, wherein the capsule shell is mainly composed of PHA and nano-micro cellulose; and the PHA is selected from one or more of P34HB3HV, P34HB5HV, P34HB, PHBV and PHBHHx.

[0006] The PHA soft capsule provided by the present invention does not need to add additives such as alum that are harmful to the human body and can solve the problem of long molding process cycle of plant soft capsules. The main degradation product of the capsule shell main component PHA, trihydroxybutyric acid, is beneficial to the human body; the specific type of PHA trimer or copolymer with a high comonomer ratio selected by the present invention has better film-forming properties, can increase the temperature resistance, does not need to be refrigerated, and does not have the problem of hard and brittle capsule shells, and does not cause oil leakage caused by softening or rupture of the capsule shell. The processing temperature is low, the energy consumption is small, and the above-mentioned PHA is amorphous and has low crystallinity, which can better control the disintegration time and accelerate the degradation rate. The present invention also has the advantages of simple production process, short molding cycle, etc., and has broad application prospects.

[0007] Preferably, the mass ratio of the PHA to the nano-micron cellulose is 20-50:1-8; preferably, the mass ratio of the PHA to the nano-micron cellulose is 25-50:1-5.

[0008] More preferably, the mass ratio of the PHA to the nano-micron cellulose is 25-28:1-2.

[0009] In the present invention, the use of the above-mentioned amount of PHA and nano-micro cellulose can give full play to the interaction between PHA and nano-micro cellulose. In particular, the use of specific PHA as the main material of the capsule and nano-micro cellulose can well solve the problem of high temperature resistance. The PHA itself is hydrophobic and does not need to be gelled. It only needs to be prepared into a paste liquid. After the capsule film is formed, it is easy to dry. For example, a capsule with a wall thickness of about 1 mm can be made by drying for only 5 to 10 minutes. And the main degradation product of PHA, trihydroxybutyric acid, is beneficial to the human body.

[0010] Preferably, the 4HB monomer content in the P34HB is 20% to 25%, and the weight average molecular weight of the P34HB is 100000 to 700000. In the present invention, the monomer content refers to the molar content unless otherwise specified.

[0011] Preferably, the HV monomer content in the PHBV is 20% to 25%, and the weight average molecular weight of the PHBV is 100,000 to 700,000.

[0012] Preferably, the HHx monomer content in the PHBHHx is 20% to 25%, and the weight average molecular weight of the PHBHHx is 100,000 to 700,000.

[0013] Preferably, the 4HB monomer content in the P34HB3HV is 20% to 25%, the 3HV monomer content is 3% to 10%, and the weight average molecular weight of the P34HB3HV is 100,000 to 700,000; and / or, the 4HB monomer content in the P34HB5HV is 20% to 25%, the 5HV monomer content is 3% to 10%, and the weight average molecular weight of the P34HB5HV is 100,000 to 700,000.

[0014] Preferably, the melting points of P34HB3HV, P34HB5HV, P34HB, PHBV and PHBHHx are 80-110°C.

[0015] Preferably, the particle size of the nano-micron cellulose is 0.1-0.5 um; preferably, the nano-micron cellulose is coniferous wood cellulose.

[0016] More preferably, the nano-micron cellulose has an octopus structure.

[0017] In the present invention, nano-micron cellulose with a particle size of 0.1 to 0.5 um is used. The nano-micron cellulose used preferably has an octopus structure, that is, a fiber similar to an octopus. The octopus structure has many branches and holes, and the branches are intricately interwoven to form a mesh structure, like an octopus, or like a broom, so that PHA particles can be better captured to form a stable emulsion state without sedimentation. In addition, the nano-micron cellulose interacts with the above-mentioned PHA at a certain dosage, which can better improve the film-forming property and increase the temperature resistance. There is no problem of hard or brittle capsule shells, and there will be no oil leakage caused by softening or rupture of the capsule shell. The processing temperature is low, the energy consumption is small, and the rubber seam rate is high. The PHA used in the present invention is amorphous and has low crystallinity, which can better control the disintegration time and accelerate the degradation rate.

[0018] More preferably, the PHA soft capsule has a rubber seam rate of ≥88%, an oil leakage rate of ≤1%, and a temperature resistance of ≥55°C.

[0019] More preferably, the thickness of the PHA soft capsule is 0.3-1 mm.

[0020] In the present invention, the capsule shell of the PHA soft capsule is spherical or elliptical, and the volume is 0.1 to 0.5 mL.

[0021] In a second aspect, the present invention provides a method for preparing the PHA soft capsule, comprising:

[0022] 1) Capsule liquid preparation: PHA, nano-micro cellulose and water are mixed and stirred in proportion to prepare capsule liquid;

[0023] 2) Pellet rolling: Add the capsule liquid and contents prepared in step 1) into a pellet rolling machine for pellet rolling and drying.

[0024] The raw materials and process for preparing the PHA soft capsules adopted by the present invention can increase the temperature resistance, do not need to be refrigerated, and do not cause the capsule shell to soften and leak oil; reduce the gelling time and the time for drying the capsule shells; the production process is simple, low-cost, and has broad application prospects.

[0025] Further preferably, in step 1), the capsule liquid comprises, by weight: 20-50 parts of PHA, 1-8 parts of nano-micron cellulose and 40-80 parts of water; preferably, 25-50 parts of PHA, 1-5 parts of nano-micron cellulose and 45-70 parts of water.

[0026] Further preferably, step 2) comprises heating the plastic box of the pelletizing machine to 60-100° C., heating the drum to 20-30° C., adding capsule liquid, setting the capsule shell thickness to 0.3-1 mm, pelletizing, and drying for 5-10 minutes.

[0027] In a third aspect, the present invention provides uses of the PHA soft capsule or the PHA soft capsule prepared by the method for preparing the PHA soft capsule, in the preparation of dietary nutritional supplements, functional foods or medicines.

[0028] Preferably, the contents of the PHA soft capsule include one or more of edible oil, cod liver oil, water-soluble vitamins and fat-soluble vitamins.

[0029] Further preferably, the content is selected from one or more of linseed oil, DHA algae oil, soybean oil, seal oil, corn oil, peanut oil, rapeseed oil, coconut oil, rice bran oil, olive oil, cod liver oil, phospholipids, vitamin E, biotin, vitamin D3, lutein and vitamin K2.

[0030] The beneficial effects of the present invention are at least that: the PHA soft capsule prepared by the present invention can increase the temperature resistance, does not need to be refrigerated, does not have the problem of hard or brittle capsule shell, and does not have oil leakage caused by softening or cracking of the capsule shell. In addition, the present invention can avoid the time of gelling and reduce the time of drying into capsule shell. At the same time, the degradation product of PHA, the main component of the capsule shell of the present invention, trihydroxybutyric acid, is beneficial to the human body. The present invention also has the advantages of simple production process, low cost, etc., and has broad application prospects. DETAILED DESCRIPTION

[0031] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0032] If no specific technology or conditions are specified in the examples, the technology or conditions described in the literature in this field or the product instructions are used. The experimental methods used in the following examples are all conventional methods unless otherwise specified. The materials, reagents, etc. used in the following examples can be obtained from commercial channels unless otherwise specified. The instruments used, etc., where the manufacturers are not specified, are all conventional products that can be purchased through regular channels.

[0033] The terms used in the present invention include PHA, which is an abbreviation for polyhydroxyalkanoate, P34HB3HV, which is an abbreviation for tripolyester of 3-hydroxybutyric acid, 4-hydroxybutyric acid and 3-hydroxyvaleric acid, P34HB5HV, which is an abbreviation for tripolyester of 3-hydroxybutyric acid, 4-hydroxybutyric acid and 5-hydroxyvaleric acid, 4HB, which is 4-hydroxybutyric acid, P34HB, which is an abbreviation for copolyester of 3-hydroxybutyric acid and 4-hydroxybutyric acid, 3HV, which is 3-hydroxyvaleric acid, PHBV, which is an abbreviation for copolyester of 3-hydroxybutyric acid and 3-hydroxyvaleric acid, HHx, which is 3-hydroxyhexanoic acid, and PHBHHx, which is an abbreviation for copolyester of 3-hydroxybutyric acid and 3-hydroxyhexanoic acid.

[0034] In the embodiment of the present invention, P34HB3HV, P34HB5HV, P34HB, PHBV, and PHBHHx are products of Beijing Microstructure Factory Biotechnology Co., Ltd. Nano-micron cellulose is made of coniferous wood cellulose, with a particle size of 0.1 to 0.5 um and an octopus structure. In the embodiment, micro-nano cellulose GMN-ZQ-600 produced by Hangzhou Greenvina Technology Co., Ltd. is specifically used.

[0035] The following examples are used to illustrate the present invention but are not intended to limit the scope of the present invention.

[0036] Example 1

[0037] Capsule liquid preparation: according to the formula, weigh 30 parts of PHA trimer (P3HB4HB3HV, 4HB monomer content is 20%, 3HV monomer content is 5%, weight average molecular weight is 400000), 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0038] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0039] Table 1 Performance test results of PHA soft capsules in Example 1

[0040] Rubber seam rate 90％ Contents 800mg Oil leakage rate ＜1％ Temperature resistance 55℃

[0041] Example 2

[0042] Capsule liquid preparation: according to the formula, weigh 30 parts of P34HB copolymer (P3HB4HB-20% 4HB, weight average molecular weight of 350000), 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0043] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0044] Table 2 Performance test results of Example 2

[0045] Rubber seam rate 88％ Contents 850mg Oil leakage rate ＜1％ Temperature resistance 60℃

[0046] Example 3

[0047] Capsule liquid preparation: according to the formula, weigh 30 parts of PHBV copolymer (PHBV-20% HV, weight average molecular weight of 400000), 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0048] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0049] Table 3 Performance test results of Example 3

[0050] Rubber seam rate 88％ Contents 810mg Oil leakage rate ＜1％ Temperature resistance 60℃

[0051] Example 4

[0052] Capsule liquid preparation: according to the formula, weigh 30 parts of PHBHHx copolymer (PHBV-20% HHx, weight average molecular weight of 700000), 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0053] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0054] Table 4 Performance test results of Example 4

[0055] Rubber seam rate 90％ Contents 800mg Oil leakage rate ＜1％ Temperature resistance 65℃

[0056] Example 5

[0057] Capsule liquid preparation: according to the formula, weigh 30 parts of P3HB4HB3HV and PHBV-20%HV (P3HB4HB3HV, 4HB monomer content is 20%, 3HV monomer content is 5%, weight average molecular weight is 400000; PHBV-20%HV, weight average molecular weight is 400000) in a mass ratio of 1:1, 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0058] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0059] Table 5 Performance test results of Example 5

[0060] Rubber seam rate 91％ Contents 820mg Oil leakage rate ＜1％ Temperature resistance 55℃

[0061] Example 6

[0062] Capsule liquid preparation: according to the formula, weigh 28 parts of PHBHHx copolymer (HHx monomer content is 22%, weight average molecular weight is 500000), 2 parts of nano-micron cellulose and 70 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0063] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0064] Table 6 Performance test results of Example 6

[0065] Rubber seam rate 95％ Contents 820mg Oil leakage rate ＜1％ Temperature resistance 65℃

[0066] Example 7

[0067] Capsule liquid preparation: according to the formula, weigh 28 parts of P34HB3Hv trimer (4HB monomer content is 21%, 3Hv monomer content is 3%, weight average molecular weight is 450000), 2 parts of nano-micron cellulose and 70 parts of water, use mechanical stirring to fully mix, stir evenly to prepare a paste liquid;

[0068] Pellet rolling process: Heat the plastic box of the pellet rolling machine (100°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0069] Table 7 Performance test results of Example 7

[0070] Rubber seam rate 94％ Contents 810mg Oil leakage rate ＜1％ Temperature resistance 63℃

[0071] Comparative Example 1

[0072] Capsule liquid preparation: according to the formula, weigh 30 parts of PHA homopolymer (PHB, weight average molecular weight of 500000), 5 parts of nano-micron cellulose and 65 parts of water, use mechanical stirring to fully mix, and stir evenly to prepare a paste liquid;

[0073] Pellet rolling process: Heat the plastic box of the pellet rolling machine (180°C), heat the drum (30°C), provide a paste liquid, add the contents, set the pellet rolling speed for pellet rolling, and then dry it for 10 minutes to dry the moisture. Use linseed oil for the contents, select the pellets, and finally package; the final thickness of the soft capsule is 0.8mm.

[0074] The PHA of Comparative Example 1 was used to prepare a capsule shell with a content of 800 mg and a rubber seam rate of 90%. The processing temperature was relatively high, and compared with Examples 1-7, the capsule shell of this comparative example was relatively hard and brittle, and was prone to cracking and oil leakage. The oil leakage rate was as high as 10%, and it could not be used for the actual production of soft capsules.

[0075] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or make equivalent replacements for some of the technical features therein. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the spirit and scope of the technical solutions of the embodiments of the present invention.

Claims

1. A PHA soft capsule, characterized in that: The PHA soft capsule comprises a capsule shell, wherein the capsule shell is mainly composed of PHA and nano-micron cellulose; the PHA is selected from one or more of P34HB3HV, P34HB5HV, P34HB, PHBV, and PHBHHx.

2. The PHA soft capsule according to claim 1, characterized in that The mass ratio of the PHA to the nano-micron cellulose is 20-50:1-8; preferably, the mass ratio of the PHA to the nano-micron cellulose is 25-50:1-5.

3. The PHA soft capsule according to claim 1 or 2, characterized in that: The 4HB monomer content in the P34HB is 20% to 25%; and / or, the HV monomer content in the PHBV is 20% to 25%; and / or, the HHx monomer content in the PHBHHx is 20% to 25%; and / or, the 4HB monomer content in the P34HB3HV is 20% to 25%, and the 3HV monomer content is 3% to 10%; and / or, the 4HB monomer content in the P34HB5HV is 20% to 25%, and the 5HV monomer content is 3% to 10%.

4. The PHA soft capsule according to any one of claims 1 to 3, characterized in that The melting points of the P34HB3HV, P34HB5HV, P34HB, PHBV and PHBHHx are 80-110°C.

5. The PHA soft capsule according to any one of claims 1 to 4, characterized in that The particle size of the nano-micron cellulose is 0.1-0.5 um; preferably, the nano-micron cellulose has an octopus structure.

6. The PHA soft capsule according to any one of claims 1 to 5, characterized in that: The rubber seam rate of the PHA soft capsule is ≥88%, the oil leakage rate is ≤1%, and the temperature resistance is ≥55° C.; and / or the thickness of the PHA soft capsule is 0.3-1 mm.

7. The PHA soft capsule according to any one of claims 1 to 6, characterized in that: The PHA soft capsule also includes contents, which include one or more of edible oil, cod liver oil, water-soluble vitamins and fat-soluble vitamins; preferably, the contents are selected from one or more of linseed oil, DHA algae oil, soybean oil, seal oil, corn oil, peanut oil, rapeseed oil, coconut oil, rice bran oil, olive oil, cod liver oil, phospholipids, vitamin E, biotin, vitamin D3, lutein and vitamin K2.

8. The method for preparing the PHA soft capsule according to any one of claims 1 to 7, characterized in that: include: 1) Capsule liquid preparation: PHA, nano-micro cellulose and water are mixed and stirred in proportion to prepare capsule liquid; 2) Adding the capsule liquid and contents prepared in step 1) into a pelletizing machine for pelletizing and drying.

9. The method for preparing the PHA soft capsule according to claim 8, characterized in that: Step 2) includes heating the plastic box of the pelletizing machine to 60-100° C., heating the drum to 20-30° C., adding capsule liquid, pelletizing, and drying for 5-10 minutes.

10. Use of the PHA soft capsule according to any one of claims 1 to 7 or the PHA soft capsule prepared by the preparation method of the PHA soft capsule according to claim 8 or 9, characterized in that: Use in preparing dietary nutritional supplements, functional foods or medicines.