CN111567805A - Water-soluble haematococcus pluvialis astaxanthin soft capsule and preparation method thereof - Google Patents

Abstract

The invention discloses a water-soluble Haematococcus pluvialis astaxanthin soft capsule and a preparation method thereof. The mass ratio of each component of the astaxanthin soft capsule wall is 100 parts of gelatin, 6 parts of citric acid and 20 parts of glycerin, 4 parts of sodium carboxymethyl cellulose, 10 parts of sorbitol, 11 to 13 parts of water, the mass percentage of each component of the capsule core is Haematococcus pluvialis astaxanthin oil 10.0-1,8.0, polyethylene glycol-400 10.0-20.0, 20.0-40.0 of mono-diglycerol unsaturated fatty acid ester, 2.0-5.0 of sorbitol, 30.0-45.0 of deca-polyglycerol monooleate, the preparation method of the astaxanthin soft capsule also includes high pressure under nitrogen protection Homogeneous mixing to prepare capsule core step. The present invention adopts all the auxiliary materials used by health food according to production needs, and the emulsifier is a processed product of unsaturated fatty acid, which is safe and non-toxic, has little health and safety risk, is compliant and legal, is suitable for the human gastrointestinal water nutrient absorption system, and can improve the active ingredient astaxanthin. bioavailability.

Description

A kind of water-soluble Haematococcus pluvialis astaxanthin soft capsule and preparation method thereof

technical field

The invention relates to a Haematococcus pluvialis astaxanthin soft capsule preparation and a preparation method thereof, in particular to a water-soluble Haematococcus pluvialis astaxanthin soft capsule and a preparation method thereof.

Background technique

Astaxanthin is an oxycarotenoid (Xanthophyll), a carotenoid containing a ketone group. Its molecular formula is C ₄₀ H ₅₂ O ₄ , the relative molecular mass is 596.86, and the semi-system designation (IUPAC) is 3,3-dihydroxy-β,β-carotene-4,4'-dione (3,3'- Dihydroxy-β,β-carotene-4,4'-dione).

Both ends of astaxanthin molecule are β terminal groups (Figure 1), containing hydroxyl and ketone groups, and its central polyolefin chain contains 9 double bonds, which can form a variety of cis-trans isomers (E/Z isomers), But in nature, it is mostly all-trans isomer (All E-isomer). In addition, astaxanthin has a chiral center at the 3 and 3' positions, so there are three optical isomers. Among the common sources of astaxanthin, Haematococcus pluvialis is the 3S, 3'S isomer, Phaffia is the 3R, 3'R isomer, and the artificial synthesis is a mixture of three isomers.

Under the condition of 100KPa, pure astaxanthin has a melting point of 216℃, a boiling point of 774℃, and a density of 1.071g/mL at 25℃. Astaxanthin is insoluble in water, soluble in most organic reagents, and has good fat solubility. Because it is an oxygenated carotenoid and has a strong polarity, it has a high saturation solubility in polar organic reagents. At 25℃ and 100KPa, the saturated solubility of astaxanthin in the four solvents of dichloromethane, chloroform, dimethyl sulfoxide and acetone are 30g/L, 10g/L, 0.5g/L and 0.2g, respectively /L. The conjugated polyene structure in the astaxanthin molecule is its chromophore and absorbs blue light, which makes its crystals and dilute solutions deep red in visible light.

The astaxanthin molecule contains a long conjugated unsaturated double bond structure, which makes it easy to destroy its structure by light, heat, and oxides. However, this structure also makes astaxanthin have strong antioxidant properties, especially free astaxanthin can quench active oxygen in a large amount. Astaxanthin can be dissolved in complex lipoproteins and adsorbed to fat moieties, and the hydroxyl and ketone groups on the ionone ring in its molecule can form astaxanthin mono- or diester with fatty acids and have stronger affinity. Fatty. Free astaxanthin can form a blue-gray complex with protein. After heating, astaxanthin can be freed and turn red.

Haematococcus pluvialis contains about 40,000mg/kg of astaxanthin, which is known to be the biological resource with the highest accumulation level of astaxanthin in nature, and also the main and best source of natural astaxanthin. The astaxanthin contained in it all exist in the form of ester, and monoester is the majority. Dry algal flour can contain more than 40 g of astaxanthin per kilogram, accounting for more than 90% (w/w) of its total carotenoid content.

Most natural astaxanthin resources exist in the form of esters, so to obtain free natural astaxanthin, the preparation process must include two steps of extraction and hydrolysis. The extraction method of astaxanthin can adopt organic solvent extraction method, or supercritical carbon dioxide fluid extraction method. There are many reports on the use of organic solvents to extract carotenoids. The use of water-soluble polar organic solvents and water-insoluble non-polar organic solvents has advantages and disadvantages. The hydrolysis of astaxanthin ester using general saponification conditions cannot meet the production requirements. This is due to the fact that a large amount of astaxanthin (Astacene) and hemi-astaxanthin will be produced during saponification of astaxanthin ester under strong alkali and aerobic conditions, and the biological function of astaxanthin is significantly different from that of astaxanthin. For this purpose, astaxanthin esters can be used directly. There is an enzyme system in the digestive tract of mammals, which can hydrolyze astaxanthin esters in the digestive tract without producing by-products, and the free astaxanthin molecules generated will enter the transport system in the body. Therefore, people can directly take astaxanthin esters to achieve the purpose of supplementing astaxanthin. In this nutritional process, the bioavailability of astaxanthin esters is a matter of concern.

Astaxanthin has powerful biological functions, mainly anti-oxidation, photoprotection, anti-cancer, enhancing immunity, maintaining eye health, maintaining central nervous system health, etc.

In vitro experiments have shown that astaxanthin is an extremely effective antioxidant with a strong quenching ability to singlet oxygen. The results show that: Astaxanthin quenches singlet oxygen at a rate 80 times that of vitamin E. Astaxanthin can also inhibit lipid peroxidation, and its ability to inhibit lipid peroxidation is 10 times that of beta-carotene and 100 times that of vitamin E. Due to its strong antioxidant capacity, astaxanthin may have positive effects on a range of unhealthy human conditions, including cardiovascular, immune system, inflammation, and neurodegeneration. As the enhancement of antioxidant mechanisms and inhibition of free radical production are considered biological pathways to prevent oxidative damage and reduce the rate of aging, astaxanthin also has anti-aging potential. At the same time, it can activate the insulin signaling pathway and upregulate the gene of FOXO3.

Studies have shown that astaxanthin can protect salmon skin from UV damage, suggesting that astaxanthin has the potential to be an edible photoprotectant. Meanwhile, studies support the hypothesis that astaxanthin can protect human tissues from oxidative and UV damage by inhibiting NF-κB activation.

Studies have shown that feeding astaxanthin in rats and mice has anti-proliferative and immune-enhancing effects on epithelial cells exposed to carcinogens, and there is a dose-response relationship. Astaxanthin has significant inhibitory effects on bladder cancer in mice, oral cancer in rats, colon cancer, and gastric cancer. Astaxanthin also has a good effect on reducing the number and volume of aflatoxin-induced liver tumor cells. Oral astaxanthin also inhibits the growth of breast cancer.

Astaxanthin has obvious immunomodulatory effects and can be used as an immune enhancer. When the mouse thymus was stimulated with antigen (TDAg), astaxanthin could significantly increase the amount of immunoglobulin M (IgM) and immunoglobulin G (IgG) in mice, and its effect was significantly higher than that of lutein. At the same time, the effect of astaxanthin on enhancing the release of interleukin-I and tumor necrosis factor α in mice was stronger than that of β-carotene and canthaxanthin. In the presence of antigens, astaxanthin can also significantly promote the production of antibodies in spleen cells and increase the production of leukocyte immunoglobulins.

When blue light acts on the human retina, the singlet oxygen and oxygen free radicals generated by photo-oxidation will cause peroxidative damage to the polyunsaturated fatty acids contained in the retina. Clinically, dietary supplementation of carotenoids can help the retina to quench reactive oxygen species, resist oxidative damage, and treat degenerative macular degeneration. As a member of carotenoids, astaxanthin can enter the fundus through the blood-brain barrier, and effectively prevent retinal oxidation and photoreceptor cell damage. It has a good effect on the treatment of degenerative macular degeneration and the protection of retinal function.

The central nervous system is rich in unsaturated fatty acids, has high metabolic activity, and is highly susceptible to oxidative damage, which leads to a variety of nervous system diseases. Astaxanthin protects the central nervous system, especially the brain and spine. It can effectively treat ischemic repetitive perfusion injury, spinal cord injury, Parkinson's syndrome, Alzheimer's disease and other central nervous system diseases.

Astaxanthin can be ingested orally, and the toxicity is very low, so far there are no reports of poisoning symptoms.

In the United States, since astaxanthin was approved by the FDA as a mixed colorant in fish feed in 2009, it has been approved for use as a single colorant in a variety of animal feeds. Haematococcus pluvialis powder (21CFR 73.185) and Rhododendron fife (21CFR 73.355) were approved in 2000 for use in fish feed to color salmon. In addition, natural astaxanthin has passed the FDA's "Generally Safe (GRAS)" certification, but its use in animal feed is strictly limited.

In the European Union, astaxanthin is approved as a new food resource (ECNo.258/97) and is recognized as a raw material for dietary supplements. Since 1997, astaxanthin has been used in five foods in EU countries, and the astaxanthin raw material in each product has been certified as substantially equivalent to the approved astaxanthin new food resource.

In China, astaxanthin was approved as a feed additive in "Feed Additives 10% Astaxanthin (GB/T 23745-2009)" in 2009. Haematococcus pluvialis was approved as a new food resource by the State Food and Drug Administration in the new resource review in 2010 (Announcement No. 17 in 2010). The daily recommended dry weight intake is ≤0.8g, but the scope of use is limited. Does not include baby food.

Adding natural astaxanthin to nutritional supplements has very practical implications for improving human health. However, astaxanthin is easily oxidatively degraded and insoluble in water, which seriously affects its bioavailability and restricts its use in pharmaceutical and food formulations. In the past 30 years, researchers have focused on improving the water solubility and stability of astaxanthin, trying to chemically modify the water-soluble solution of astaxanthin.

Chinese invention patent CN 101367837B discloses a novel astaxanthin derivative, specifically an astaxanthin phosphate derivative and a preparation method thereof. The water-solubility of the derivative is enhanced, and the present invention can be used in the fields of medicine and health food.

Chinese invention patent CN 105646869B also discloses a water-soluble astaxanthin derivative, specifically astaxanthin succinate PEG derivative and a preparation method thereof. The astaxanthin succinic acid diester PEG derivative prepared by the present invention has good water solubility, greatly improves the application range of astaxanthin, and can be used as a food additive in meat products and aquatic products, because it has good resistance to Oxidation can be used in cosmetics and pharmaceutical products, and can also be added to health food as a functional factor.

However, since the U.S. Food and Drug Administration (FDA) prohibits chemically synthesized astaxanthin from entering the food and dietary supplement market, synthetic astaxanthin and its derivatives are mainly used in the fields of aquaculture and daily chemicals.

The use of water-soluble molecules to physically encapsulate astaxanthin can solve the application defects of astaxanthin insoluble in water and poor stability. The key is to improve the encapsulation rate of astaxanthin by hydrophilic micro/nano carriers. Various micro/nano encapsulation technologies have been reported for the preparation of water-soluble astaxanthin products, such as condensed phase separation technology, host-guest inclusion complex technology, nanoprecipitation, emulsification solvent evaporation technology, supercritical fluid technology , Microencapsulation technology, etc.

Soft capsule refers to the direct encapsulation of a certain amount of liquid drugs, or the dissolution or dispersion of solid drugs in suitable excipients to make solutions, suspensions, emulsions or semi-solids, and sealed in spherical or elliptical soft capsules. Capsules in capsules.

Soft capsules have significant advantages: (1) Liquid oily substances can be directly encapsulated in capsules, without the use of additives such as adsorption and inclusion, and the content of oily substances in soft capsules is as high as 60% to 85% (weight), while the inclusion of The general content of the material is below 50%. (2) If the film is made of thick gelatin, it can be completely air-sealed, the capsule strength and the film blocking property are high, and the content can be kept stable for a long time. According to the measurement, the oxygen barrier property of gelatin film is more than 30 times higher than that of polyethylene film. It is very stable to oxygen in the air and can prevent air oxidation and moisture absorption. (3) After ingestion, the contents are quickly released, and the utilization rate and absorption rate in the body are high. (4) The content uniformity is good, and the content deviation is very low. (5) It can cover the odor and odor of certain contents, especially for some functional health foods and pharmaceuticals. Because it is different from ordinary food, there are many odor and odor components. (6) The taste, color, fragrance, transparency and gloss of the capsule film can be freely selected. Compared with other round products, the appearance is glossy and eye-catching. (7) The round air-tight container is a kind of purification type container, which can not be mixed with foreign matter when it is circulated after it is made. (9) There is no need to add additives such as binders and molding agents. Generally, soft capsules are made of gelatin, glycerin and water, and are edible natural products.

Chinese invention patents CN 106923334A, CN 108902958A, CN 109349553A and CN 109481416A all disclose an astaxanthin soft capsule. However, in these soft capsule preparations, the content of the capsule core is a fat-soluble composition or a fat-soluble suspension composition, which is not dispersed in water and aggregates into oil droplets, which is not conducive to the transportation and absorption of the human gastrointestinal aqueous nutrient absorption system.

Chinese invention patent CN103011282A discloses an astaxanthin self-emulsifying soft capsule preparation and a preparation method thereof. The components of the astaxanthin self-emulsifying soft capsule preparation and their mass ratios are as follows: astaxanthin raw material: oil phase: emulsifier: auxiliary The emulsifier is 1:20～60:10～70:0:30; the oil phase adopts natural vegetable oil or fatty acid ester, the emulsifier adopts non-ionic emulsifier, and the auxiliary emulsifier adopts medium chain alcohol or short chain alcohol. Self-emulsifying in vivo. The patent uses a large number of non-ionic active agents, which are not in the "Catalogue of Excipients for Health Food Filing Products and the Regulations for Use", which have great health and safety risks, and do not meet the regulations for the use of excipients in health food. Secondly, the raw material of astaxanthin is astaxanthin There is also the suspicion of using synthetic astaxanthin, which is illegal and illegal.

Chinese invention patent CN 107050066A discloses an astaxanthin-kelp self-emulsifying soft capsule and its preparation method and application. The mass fraction of each component is: astaxanthin 0.1-5%, kelp extract 0.2-8%, non- 18-63% of ionic surfactant, 2-5% of co-surfactant and olive oil to make up to 100%; the non-ionic surfactant is Tween 85 and nonylphenol polyoxyethylene ether np-40; both The weight ratio is 1:10-10:1; the co-surfactant is a mixture of one or two of glycerol and polyethylene glycol. Polyoxyethylene-containing surfactants have the disadvantage of dissolving erythrocyte membranes and producing hemolysis. They are used in large quantities and do not meet the requirements of the "Catalogue and Use Regulations of Health Food Filing Products Excipients", and the raw material of astaxanthin is astaxanthin. There is a suspicion of using synthetic astaxanthin, which is illegal and illegal.

Chinese invention patent CN 109893513A The invention discloses a composite Haematococcus pluvialis astaxanthin self-emulsifying soft capsule and its preparation method and application. The soft capsule comprises a capsule core and a capsule wall, and the capsule core comprises Haematococcus pluvialis astaxanthin or its extract, vegetable oil, emulsifier, co-emulsifier and antioxidant. This patent uses Haematococcus pluvialis astaxanthin as astaxanthin monomer, which is unstable and may be contaminated by isomerism, oxidation or degradation products. Haematococcus pluvialis extract is used, which has many impurities. , there are still large health and safety risks.

The use of supplementary materials for health food filing products should comply with relevant national standards and regulations, and must follow the following principles: do not cause any health hazard to the human body; do not cover the spoilage of the product; Or for the purpose of adulteration, adulteration and forgery; do not reduce the health function and nutritional value of the product itself; reduce the amount used in the product as much as possible under the premise of achieving the expected effect; the use of processing aids should comply with the "Food Safety" National Standard for the Use of Food Additives (GB2760) and related regulations.

The use of excipients in food form products shall comply with relevant regulations such as the "National Food Safety Standard for the Use of Food Additives" (GB2760); the use of food raw materials included in the "Regulations on the Use of Excipients for Health Food Filing Products and Their Use (Trial)" is allowed.

SUMMARY OF THE INVENTION

In view of the deficiencies of the prior art, the object of the present invention is to provide a safe, non-toxic, compliant water-soluble Haematococcus pluvialis astaxanthin soft capsule that can be dispersed into an oil-in-water emulsion in water and a preparation method thereof .

To achieve the above object, the present invention provides the following technical solutions:

A water-soluble Haematococcus pluvialis astaxanthin soft capsule, comprising a capsule wall and a capsule core, the capsule wall is a water-soluble composition composed of gelatin, a plasticizer and water, and the capsule core is Haematococcus pluvialis astaxanthin oil , a self-emulsifying composition composed of mono-diglycerol fatty acid ester, polyglycerol fatty acid ester, polyethylene glycol-400, and sorbitol, which can spontaneously form an oil-in-water emulsion in water, and the Haematococcus pluvialis shrimp The astaxanthin oil contains astaxanthin monoester and diester, and the astaxanthin is mainly all-trans L-astaxanthin, and it is characterized in that the capsule wall water-soluble composition plasticizer is glycerol, sorbitol, citric acid The composition with sodium carboxymethyl cellulose, the water-soluble composition component of capsule wall and its mass fraction are:

The mono- and diglycerol fatty acid esters of the capsule core self-emulsifying composition are mono-diglycerol unsaturated fatty acid esters with an HLB value of 4-6, and the polyglycerol fatty acid esters of the capsule core self-emulsifying composition are decapolymers with an HLB value of more than 13 Glycerol monooleate, the components of the capsule core self-emulsifying composition and their mass percentages are:

In order to enable the capsule core self-emulsifying composition to spontaneously form a transparent nanoemulsion in water, its components and their mass percentages are preferably:

The above-mentioned Haematococcus pluvialis astaxanthin oil is preferably the Haematococcus pluvialis astaxanthin oil prepared by the artificial cultivation of Haematococcus pluvialis extract through physical refining, purification and blending, and the mass percentage of monoester in the astaxanthin ester is 70-75, The mass percentage of diester is 25-30, and the mass percentage of astaxanthin in the existing state of more than 90% is all-trans-L-astaxanthin.

Further, one or more species mixtures in the above-mentioned Haematococcus pluvialis extract physical refining, purification and reconciliation process can be added to make red globules by adding fat-soluble vitamins, fat-soluble pigments or the animal and vegetable oils with health care function. Algal astaxanthin oil, supplements the physiological effects of Haematococcus pluvialis astaxanthin.

The above-mentioned mono-diglycerol unsaturated fatty acid esters are preferably mono-diglycerol unsaturated fatty acid esters with a monoglyceride mass percentage ≥ 90.0, including mono-diglycerol oleate, mono-diglycerol linoleate, mono-diglycerol linoleate A mixture of one or more of them.

The above-mentioned water-soluble Haematococcus pluvialis astaxanthin soft capsule can be applied on the gel candy. First, the soft capsule wall skin is prepared, the soft capsule wall skin is laid flat on the groove mold, and the core self-emulsifying composition is injected into the capsule. , and then press another layer of soft capsule wall skin, and roll and combine to form a sandwich-type gel candy.

The preparation method of the above-mentioned water-soluble Haematococcus pluvialis astaxanthin soft capsule, comprising the steps of gelatinizing, making pills, shaping, washing pills, drying, inspecting pills, inspecting, and packaging, and also comprising preparing the capsule core under nitrogen protection The steps of the self-emulsifying composition and the steps of preparing the capsule-core self-emulsifying composition include the following operations in sequence: first, according to the formula requirements of the component mass percentage, accurately weigh the required components, and sequentially put them into a pre-nitrogen-filled stirring and mixing tank , mixed, and then transferred to a high-pressure homogenizer for homogenization, and the qualified capsule core self-emulsifying composition after homogenization was transferred to a pre-nitrogen-filled stirring storage tank for use in the soft capsule pelleting step.

In the above-mentioned steps of preparing the capsule core self-emulsifying composition, the preferred process conditions are that the mixing temperature is 25°C to 35°C, the mixing time is 20min to 30min, the pressure of the primary valve of the homogenizer is 25MPa to 30MPa, and the pressure of the secondary valve is 25 MPa to 30 MPa. 5MPa～10MPa, 2 times of homogenization, 25MPa～30MPa of homogenization pressure, 2 times of homogenization, the partial pressure of oxygen in the mixing kettle and the storage tank is 200Pa～300Pa.

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

1. in the water-soluble composition of the soft capsule wall of the present invention, the plasticizer is the composition of glycerol, sorbitol, citric acid and sodium carboxymethyl cellulose, with respect to 100 parts of dry gelatin, the mass fraction is 20:10 :6:4, the plasticizer composition can significantly improve the disintegration rate of the soft capsule wall and keep it within 30 minutes. The hydrolyzate is weakly acidic in water, which makes the gelatin positively charged, which is beneficial to the transportation and absorption of the negatively charged system in the small intestine of the human body, and improves the bioavailability of the active ingredient astaxanthin in the soft capsule. The excipients used in the appropriate amount according to the production needs in the “Regulations on Available Excipients for Food Filing Products and Their Use” are safe and non-toxic, with low health and safety risks, and are compliant and legal.

2. The self-emulsifying composition of the soft capsule core of the present invention can self-emulsify into an oil-in-water emulsion in water, and the improved solution can be emulsified into a transparent nano-solution, adapting to the human gastrointestinal water nutrient absorption system, and improving the active ingredient of the soft capsule. The bioavailability of astaxanthin, and all the components of the soft capsule core are also the excipients used in appropriate amounts according to production needs in the "Regulations on the Available Excipients of Health Food Filing Products and Their Use", which are safe and non-toxic, with low health and safety risks, and are suitable for Legal.

3. The self-emulsifying composition of the soft capsule core of the present invention adopts Haematococcus pluvialis astaxanthin oil as the Haematococcus pluvialis astaxanthin oil prepared by the artificial cultivation of Haematococcus pluvialis extract through physical refining and purification, and the astaxanthin oil is The mass percentage of monoester is 70-75, the mass percentage of diester is 25-30, and the mass percentage of astaxanthin in the existing state is more than 90% of all-trans-L-astaxanthin. The processed Haematococcus pluvialis extract avoids possible isomerization, oxidation and degradation product pollution during the deep processing of astaxanthin monomer, and also avoids the influence of excessive impurities in the initially processed Haematococcus pluvialis extract , more healthy and safe, and more favorable to exert the biological activity of astaxanthin. The emulsifier used in the capsule core self-emulsifying composition is the deep-processed product of unsaturated fatty acids of oleic acid, linoleic acid and linolenic acid, which can promote the transportation and absorption of fat-soluble astaxanthin, and itself is a high-quality source of unsaturated fatty acids. The capsule core self-emulsifying composition has less emulsifier in the narrow sense, and only less than 20% of the co-emulsifier is left, and the health and safety risk is very low.

4. The preparation method of the water-soluble Haematococcus pluvialis astaxanthin soft capsule of the present invention adopts the self-emulsifying composition of the homogeneously mixed capsule core under nitrogen protection, and temporarily stores it under nitrogen protection, and does not use the anti-oxidant added. This measure is conducive to maintaining the balance of the antioxidant system of astaxanthin oil. Practice has proved that high-pressure homogeneous mixing under nitrogen protection is more conducive to ensuring the stability and consistency of the self-emulsifying composition of the capsule core.

Description of drawings

Figure 1 Molecular structure of all-trans astaxanthin.

Figure 2 Molecular structure of Haematococcus pluvialis astaxanthin mono- and diester.

Detailed ways

The invention discloses a water-soluble Haematococcus pluvialis astaxanthin soft capsule, comprising a capsule wall and a capsule core, wherein the capsule wall is a water-soluble composition composed of gelatin, a plasticizer and water, and the capsule core is a red globule of pluvialis Self-emulsifying composition composed of algal astaxanthin oil, mono-diglycerol fatty ester, polyglycerol fatty acid ester, polyethylene glycol-400, sorbitol, can spontaneously form oil-in-water emulsion in water, pluvialis red ball The algal astaxanthin oil contains astaxanthin mono- and di-ester, the astaxanthin is mainly all-trans astaxanthin, and the plasticizers of the water-soluble composition of the capsule wall are glycerol, sorbitol, citric acid and carboxymethyl cellulose The composition of sodium, the self-emulsifying composition of the capsule core, the mono-diglycerol fatty acid esters are mono-diglycerol unsaturated fatty acid esters with an HLB value of 4-6, and the polyglycerol fatty acid esters of the capsule core self-emulsifying composition are ten HLB values above 13. Polyglycerol monooleate, the above-mentioned capsule wall and capsule core components are all the excipients used in appropriate amounts according to production needs in the "Regulations on Available Excipients for Health Food Filing Products and Their Use", which are safe and non-toxic, with low health and safety risks, and are compliant and legal. .

The Haematococcus pluvialis astaxanthin oil is preferably the Haematococcus pluvialis astaxanthin oil prepared by the artificial cultured Haematococcus pluvialis extract through physical refining, purification and blending. The mass percentage of the ester is 25-30, and the mass percentage of the astaxanthin in the existing state of more than 90% is all-trans astaxanthin. These characters are the basic characteristics that distinguish Haematococcus pluvialis astaxanthin oil astaxanthin from other sources of astaxanthin, such as shrimp and crab scraps, Phaffia rhodozyma and synthetic astaxanthin as well as deep-processed astaxanthin monomer , the molecular structure of Haematococcus pluvialis astaxanthin mono- and diester is shown in Figure 2. Haematococcus pluvialis astaxanthin oil source astaxanthin exists in an esterified state. Compared with astaxanthin monomer, it is stable and easy to obtain, and has the same physiological effect.

In order to further supplement the physiological efficacy of Haematococcus pluvialis astaxanthin, one of fat-soluble vitamins, fat-soluble pigments or animal and vegetable oils with health-care functions can be added in the process of physical refining, purification and reconciliation of the Haematococcus pluvialis extract. A mixture of one or more species is used to make Haematococcus pluvialis astaxanthin oil.

In order to further improve the emulsifying performance of astaxanthin oil, the mass percentage of monoglyceride in the mono-diglycerol unsaturated fatty acid ester should be ≥90.0.

Water-soluble Haematococcus pluvialis astaxanthin soft capsules can also be applied to sandwich-type gel candies. First, the skin of the soft capsule is prepared, the skin of the soft capsule is laid flat on the groove mold, and injected into the core to self-emulsify. The composition is then pressed with another layer of soft capsule wall skin, and rolled to form a sandwich-type gel candy.

The preparation method of water-soluble Haematococcus pluvialis astaxanthin soft capsule includes the preparation steps of gelatinization, pill making, shaping, pill washing, drying, pill inspection, inspection and packaging. First, gelatinization, measuring dry gelatin 0.7-1.4 times the mass of water, heat, add plasticizer, dissolve completely, then add gelatin, stir to dissolve, degas under negative pressure, filter and remove impurities to obtain glue; then make pellets, either by molding method or drop method; Regardless of whether it is a soft capsule made by pressing or dropping, it needs to be shaped, washed, and dried until the water content is below 9.0% by mass; then, the pills are inspected to remove unqualified products; finally, the products are inspected and packaged according to the product implementation standards. .

In view of the fact that the core of the water-soluble Haematococcus pluvialis astaxanthin soft capsule is composed of Haematococcus pluvialis astaxanthin oil, mono- and diglyceride fatty esters, polyglycerol fatty acid esters, polyethylene glycol-400, and sorbitol. The self-emulsifying composition has super strong oxidation resistance, so it is necessary to homogenize the capsule core self-emulsifying composition under nitrogen protection. Firstly, according to the formula requirements of the component mass percentage, accurately weigh the required components, put them into a pre-nitrogen-filled stirring mixing tank in turn, mix them, and then put them into a high-pressure homogenizer for homogenization. After homogenization, the qualified capsule core self-emulsifying combination The material is transferred into a stirring storage tank filled with nitrogen in advance, and is used in the step of making soft capsules.

The present invention will be described in further detail below in conjunction with specific embodiments.

Example

Example 1

Preparation of a water-soluble Haematococcus pluvialis astaxanthin soft capsule

1) Formula of capsule wall components (mass meter)

100 parts of gelatin, 20 parts of glycerin, 10 parts of sorbitol, 6 parts of citric acid, 4 parts of sodium carboxymethyl cellulose, and 110 parts of water.

2) Component formula of capsule core (mass percentage)

Haematococcus pluvialis astaxanthin oil 10.0%, mono-diglycerol oleate (mass percentage of monoglyceride ≥ 90.0) 20.0%, ten polyglycerol monooleate 45.0%, polyethylene glycol-400 20.0%, sorbose Alcohol 5.0%.

3) glue

Measure 1.1 times the mass of dry gelatin in water, heat, add glycerin, sorbitol, citric acid, and sodium carboxymethyl cellulose required for the formula, dissolve completely, then add the gelatin required for the formula, stir to dissolve, degas under negative pressure, and filter Remove impurities to get glue.

4) Preparation of capsule core

Firstly, according to the formula requirements of the component mass percentage, accurately weigh the required components, and then put them into a pre-nitrogen-filled stirring and mixing kettle. Homogenization, the pressure of the first valve is 25MPa, the pressure of the second valve is 10MPa, and the homogenization is performed twice. After homogenization, the qualified capsule core self-emulsifying composition is transferred into the stirring storage tank filled with nitrogen in advance, and the oxygen partial pressure in the storage tank is 300Pa to obtain the capsule core composition.

5) Preparation of pills, shaping, washing pills, drying, pill inspection, inspection and packaging, and preparing with conventional soft capsules to obtain water-soluble Haematococcus pluvialis astaxanthin soft capsules.

Randomly extract 1 soft capsule, cut the wall of the capsule, drop the contents of the capsule core into 150 mL of warm water at 35°C to 40°C, shake gently to obtain a red emulsion.

Randomly extract 1 soft capsule, put it directly into 150mL of warm water at 35℃～40℃, disintegrate completely in 25 minutes, shake gently to get a red emulsion, the pH of the emulsion is 4.50, drop into 10% gum arabic solution, there are cohesive floccules The gum arabic solution is a negatively charged colloid, indicating that the emulsion is positively charged.

Example 2

Preparation of a water-soluble Haematococcus pluvialis astaxanthin soft capsule

1) Formula of capsule wall components (mass meter)

100 parts of gelatin, 20 parts of glycerin, 10 parts of sorbitol, 6 parts of citric acid, 4 parts of sodium carboxymethyl cellulose, and 100 parts of water.

2) Component formula of capsule core (mass percentage)

Haematococcus pluvialis astaxanthin oil 18.0%, mono-diglycerol linoleate (mass percentage of monoglycerides ≥ 90.0) 40.0%, ten polyglycerol monooleate 30.0%, polyethylene glycol-400 10.0%, sorbitan Sugar alcohol 2.0%.

3) glue

Measure 1.0 times the mass of dry gelatin in water, heat, add glycerin, sorbitol, citric acid, and sodium carboxymethyl cellulose required for the formula, dissolve completely, then add the gelatin required for the formula, stir to dissolve, degas under negative pressure, and filter Remove impurities to get glue.

4) Preparation of capsule core

Firstly, according to the formula requirements of the component mass percentage, accurately weigh the required components and put them into a pre-nitrogen-filled stirring and mixing tank in turn. The oxygen partial pressure in the mixing tank is 300Pa, and mix at 30°C for 30min, and then put into a high-pressure homogenizer for Homogenization, the pressure of the first valve is 30MPa, the pressure of the second valve is 10MPa, and the homogenization is performed twice. After homogenization, the qualified capsule core self-emulsifying composition is transferred to the stirring storage tank filled with nitrogen in advance. The oxygen partial pressure in the storage tank is 200Pa to obtain the capsule core composition.

5) Preparation of pills, shaping, washing pills, drying, pill inspection, inspection and packaging, and preparing with conventional soft capsules to obtain water-soluble Haematococcus pluvialis astaxanthin soft capsules.

Randomly extract 1 soft capsule, cut the wall of the capsule, drop the contents of the capsule core into 150 mL of warm water at 35°C to 40°C, shake gently to obtain a red emulsion.

Randomly extract 1 soft capsule, directly put it into 150mL of warm water at 35℃～40℃, disintegrate completely in 27 minutes, shake gently to get a red emulsion, the pH of the emulsion is 4.60, drop into 10% gum arabic solution, there are agglomerated floccules. The gum arabic solution is a negatively charged colloid, indicating that the emulsion is positively charged.

Example 3

Preparation of a water-soluble Haematococcus pluvialis astaxanthin soft capsule

1) Formula of capsule wall components (mass meter)

100 parts of gelatin, 20 parts of glycerin, 10 parts of sorbitol, 6 parts of citric acid, 4 parts of sodium carboxymethyl cellulose, 120 parts of water.

2) Component formula of capsule core (mass percentage)

Haematococcus pluvialis astaxanthin oil 15.0%, mono-diglycerol oleate (mass percent of monoglycerides ≥ 90.0) 16.0%, mono-diglycerol linoleate (mass percent of monoglycerides ≥ 90.0) 16.0%, ten poly Glycerol monooleate 35.0%, Macrogol-400 14.0%, Sorbitol 4.0%.

3) glue

Measure 1.2 times the mass of dry gelatin in water, heat, add glycerin, sorbitol, citric acid, sodium carboxymethyl cellulose required for the formula, dissolve completely, then add the gelatin required for the formula, stir to dissolve, degas under negative pressure, filter Remove impurities to get glue.

4) Preparation of capsule core

Firstly, according to the formula requirements of the component mass percentage, accurately weigh the required components, and then put them into a pre-nitrogen-filled stirring and mixing kettle. Homogenization, the pressure of the first valve is 25MPa, the pressure of the second valve is 5MPa, and the homogenization is performed twice. After homogenization, the qualified capsule core self-emulsifying composition is transferred into the stirring storage tank filled with nitrogen in advance, and the oxygen partial pressure in the storage tank is 250Pa to obtain the capsule core composition.

5) Preparation of pills, shaping, washing pills, drying, pill inspection, inspection and packaging, and preparing with conventional soft capsules to obtain water-soluble Haematococcus pluvialis astaxanthin soft capsules.

Randomly extract 1 soft capsule, cut the wall of the capsule, drop the contents of the capsule core into 150mL of warm water at 35°C to 40°C, shake gently to get a red transparent solution, the water-in-oil emulsion is transparent, and the particle size of the emulsion is nanometers. grade, the emulsion is a nanoemulsion.

Randomly extract 1 soft capsule, put it directly into 150mL of warm water at 35℃～40℃, disintegrate completely in 30 minutes, shake gently to get a red translucent emulsion, the emulsion pH is 4.50, drop into 10% gum arabic solution, there is agglomeration The gum arabic solution is a negatively charged colloid, indicating that the emulsion is positively charged.

Example 4

Preparation of a water-soluble Haematococcus pluvialis astaxanthin soft capsule

1) Formula of capsule wall components (mass meter)

100 parts of gelatin, 20 parts of glycerin, 10 parts of sorbitol, 6 parts of citric acid, 4 parts of sodium carboxymethylcellulose, 140 parts of water.

2) Component formula of capsule core (mass percentage)

Haematococcus pluvialis astaxanthin oil 13.0%, mono-diglycerol oleate (mass percentage of monoglycerides ≥ 90.0) 12.0%, mono- and diglycerol linoleate (mass percentage of monoglycerides ≥ 90.0) 12.0%, mono- and diglycerides Glycerol linolenic acid ester (mass percentage of monoglyceride ≥ 90.0) 3.0%, ten polyglycerol monooleate 40.0%, polyethylene glycol-400 14.0%, sorbitol 4.0%.

3) glue

Measure 1.4 times the mass of dry gelatin in water, heat, add glycerin, sorbitol, citric acid, sodium carboxymethyl cellulose required for the formula, dissolve completely, then add the gelatin required for the formula, stir to dissolve, degas under negative pressure, filter Remove impurities, get glue.

4) Preparation of capsule core

Firstly, according to the formula requirements of the component mass percentage, the required components are accurately weighed, and then put into a pre-nitrogen-filled stirring and mixing tank in turn. The oxygen partial pressure in the mixing tank is 300Pa, and the mixture is mixed at 35 °C for 25 minutes, and then put into a high-pressure homogenizer. Homogenization, the pressure of the primary valve is 25 MPa, the pressure of the secondary valve is 10 MPa, and the homogenization is performed twice. After homogenization, the qualified capsule core self-emulsifying composition is transferred to the stirring storage tank filled with nitrogen in advance. The oxygen partial pressure in the storage tank is 200Pa to obtain the capsule core composition.

5) Preparation of pills, shaping, washing pills, drying, pill inspection, inspection and packaging, and preparing with conventional soft capsules to obtain water-soluble Haematococcus pluvialis astaxanthin soft capsules.

Randomly extract 1 soft capsule, cut the wall of the capsule, drop the contents of the capsule core into 150mL of warm water at 35°C to 40°C, shake gently to get a red transparent solution, the water-in-oil emulsion is transparent, and the particle size of the emulsion is nanometers. grade, the emulsion is a nanoemulsion.

Randomly extract 1 soft capsule, directly put it into 150mL of warm water at 35℃～40℃, disintegrate completely in 28 minutes, shake gently to get a red translucent emulsion, the emulsion pH is 4.40, drop into 10% gum arabic solution, there is agglomeration The gum arabic solution is a negatively charged colloid, indicating that the emulsion is positively charged.

The above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the scope of the present invention. within the scope of protection.

In addition, it should be understood that although this specification is described in terms of embodiments, not each embodiment only includes an independent technical solution, and this description in the specification is only for the sake of clarity, and those skilled in the art should take the specification as a whole , the technical solutions in each embodiment can also be appropriately combined to form other implementations that can be understood by those skilled in the art.

Claims (8)

1. A water-soluble haematococcus pluvialis astaxanthin soft capsule comprises a capsule wall and a capsule core, wherein the capsule wall is a water-soluble composition consisting of gelatin, a plasticizer and water, the capsule core is a self-emulsifying composition consisting of haematococcus pluvialis astaxanthin oil, mono-diglycerol fatty ester, polyglycerol fatty acid ester, polyethylene glycol-400 and sorbitol, an oil-in-water emulsion can be spontaneously formed in the water, the haematococcus pluvialis astaxanthin oil contains astaxanthin monoester and diester, the water-soluble composition plasticizer for the capsule wall is a composition consisting of glycerol, sorbitol, citric acid and sodium carboxymethylcellulose, and the water-soluble composition for the capsule wall comprises the following components in parts by mass:

the capsule core self-emulsifying composition comprises the following components in percentage by mass:

2. the water-soluble haematococcus pluvialis astaxanthin soft capsule according to claim 1, characterized in that the capsule core self-emulsifying composition comprises the following components in percentage by mass:

3. the water-soluble haematococcus pluvialis astaxanthin soft capsule according to claim 1 or 2, characterized in that the haematococcus pluvialis astaxanthin oil is the haematococcus pluvialis astaxanthin oil prepared by physically refining, purifying and blending an artificially cultured haematococcus pluvialis extract, wherein the mass percent of monoester in astaxanthin ester is 70-75, the mass percent of diester is 25-30, and more than 90% of astaxanthin in an occurrence state is all-trans astaxanthin.

4. The water-soluble haematococcus pluvialis astaxanthin soft capsule according to claim 3, wherein the haematococcus pluvialis extract is subjected to physical refining, purification and blending, and one or more of fat-soluble vitamins, fat-soluble pigments and animal and vegetable fats and oils with health care functions are added to prepare the haematococcus pluvialis astaxanthin oil.

5. The soft capsule of water-soluble haematococcus pluvialis astaxanthin according to claim 1 or 2, characterized in that the mass percentage of monoglycerides in the monodiglycerol unsaturated fatty acid esters is equal to or more than 90.0, comprising a mixture of one or more of mono-diglycerol oleate, mono-diglycerol linoleate, and mono-diglycerol linolenate.

6. The use of a soft capsule of water-soluble haematococcus pluvialis astaxanthin according to claim 1, wherein the gel candy is prepared by first preparing a soft capsule wall skin, laying a layer of the soft capsule wall skin on a groove die, injecting the core self-emulsifying composition, then laying a layer of the soft capsule wall skin, and rolling and combining the layers.

7. The method for preparing the water-soluble haematococcus pluvialis astaxanthin soft capsule of claim 1, comprising the steps of gelatin melting, pelleting, sizing, pill washing, drying, pill inspection, inspection and packaging of conventional soft capsule preparation, and further comprising the step of preparing the capsule core self-emulsifying composition under the protection of nitrogen, wherein the step of preparing the capsule core self-emulsifying composition comprises the following operations: accurately weighing the required components according to the requirements of the formula of the mass percent of the components, sequentially putting the components into a stirring and mixing kettle which is filled with nitrogen in advance, mixing, then putting the components into a high-pressure homogenizer for homogenization, transferring the qualified capsule core self-emulsifying composition into a stirring storage tank which is filled with nitrogen in advance after the homogenization, and preparing the soft capsule for pill making.

8. The method for preparing a soft capsule of water-soluble haematococcus pluvialis astaxanthin according to claim 7, wherein in the step of preparing the capsule core self-emulsifying composition, the mixing temperature is 25-35 ℃, the mixing time is 20-30 min, the pressure of a first-stage valve of a high-pressure homogenizer is 25-30 MPa, the pressure of a second-stage valve of the high-pressure homogenizer is 5-10 MPa, the homogenization is carried out for 2 times, and the oxygen partial pressure in a mixing kettle and a storage tank is 200-300 Pa.

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