Krill oil soft capsule helpful for improving bone mineral density

Abstract

The invention provides a krill oil soft capsule helpful for improving bone mineral density, and belongs to the technical field of biological pharmacy. The content of the krill oil soft capsule comprises 85-90 parts of krill oil, 7-10 parts of colostrum basic protein, 200 parts of oyster calcium, 375-379 parts of perilla seed oil and 28 parts of beewax. The invention also discloses a preparation method of the krill oil soft capsule. The soft capsule prepared by the invention is good in content flowability and uniformity, and the pressed soft capsule product is stable in quality and high in yield.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of biological medicine, and particularly relates to a phosphorus shrimp oil soft capsule which is helpful to improve bone density. BACKGROUND

[0002] Bone mineral density is the main index of bone strength, an important marker of bone quality, and an important basis for reflecting the degree of osteoporosis and predicting the risk of fracture. The bone density of a human being reaches a peak at about 30 years old and then decreases year by year due to bone loss with the increase of age. It is reported that the amount of bone loss is generally 20-30% of the peak value, and the maximum can reach 40% after 60 years old, regardless of men and women. With the increase of age, compared with young people under 30 years old under the same nutritional conditions, middle-aged and old people still inevitably have a large amount of bone loss, a decrease in bone density, a decrease in bone strength, and gradually become porous and easy to break, so that middle-aged and old people often have unprovoked fractures due to osteoporosis caused by a decrease in bone density. Nowadays, people pay more and more attention to the quality of life, enhance the ability to delay aging, increase bone density and strength, and delay the health care drugs of human body aging, and thus the development of health care food for increasing bone density and delaying aging is very necessary and has positive practical significance.

[0003] Antarctic krill is a small crustacean with a body length of up to 6 cm and a lifespan of 5-6 years, and is the largest single species of biomass in the world. Krill oil is naturally rich in EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), as well as choline, phospholipids and astaxanthin, and is a very good raw material for nutritional and health care food, which is rich in super antioxidant astaxanthin, Omega-3 fatty acids and phospholipids. Omega-3 fatty acids can promote osteoblast differentiation and maturation, while inhibiting osteoclast activity, thereby increasing bone density. Phospholipid Omega-3 is more easily absorbed by the human body, promotes calcium absorption, regulates bone marrow mesenchymal stem cell function, and promotes bone formation. The antioxidant effect of astaxanthin can also protect bone cells from free radical damage.

[0004] Alkaline protein generally refers to alkaline protein, and alkaline protein generally refers to protein with pH greater than 7 under isoelectric point conditions. Colostrum alkaline protein can directly act on bone cells, and can also promote normal metabolism of bone, maintain dynamic balance of cells, promote faster growth and development of bone, and also can repair its own bone quality.

[0005] The phosphorus shrimp oil is matched with the basic protein, the anti-inflammatory environment of the phosphorus shrimp oil can improve the sensitivity of the basic protein to the osteoblast, and the osteogenesis of the basic protein further depends on the DHA provided by the phosphorus shrimp oil to maintain the cell membrane fluidity. The oyster powder is matched with the phosphorus shrimp oil, the calcium zinc of the oyster powder is combined with the phospholipid of the phosphorus shrimp oil to form a lipid-mineral complex, which promotes the transmembrane transport and the intrabone deposition. The phosphorus shrimp oil, the basic protein and the oyster powder realize the positive balance of the bone metabolism through the triple path of "inhibiting bone resorption (phosphorus shrimp oil)-promoting bone formation (basic protein)-providing mineralization raw materials (oyster powder)".

[0006] In the prior art, oil products are usually sold to the terminal in the form of soft capsules, that is, a certain amount of Antarctic krill oil is packaged in a soft capsule shell of various shapes to obtain an Antarctic krill oil soft capsule. The calcium carbonate in the content of the soft capsule is heavy and prone to stratification, and usually needs to add beeswax as a suspending agent. After adding beeswax to the content, stratification and precipitation of beeswax, poor flowability and other problems are prone to occur, resulting in unstable filling amount of the soft capsule during filling, affecting the yield of the finished soft capsule. Patent CN201711316031.8 discloses a soft capsule containing astaxanthin, the content of the soft capsule includes astaxanthin, calcium carbonate, edible oil and beeswax, the weight fractions are 75-85 parts, 295-320 parts, 120-140 parts and 12-15 parts respectively, wherein the astaxanthin is astaxanthin oil; the content of the soft capsule is a suspension with high solid content, and has good uniformity and physical stability. SUMMARY

[0007] The purpose of the present application is to provide a phosphorus shrimp oil soft capsule with good content flowability, uniform and stable quality, which can help improve bone density.

[0008] The technical solution of the present application is: a phosphorus shrimp oil soft capsule which can help improve bone density, the content includes 85-90 parts of phosphorus shrimp oil, 5-15 parts of colostrum basic protein, 200 parts of oyster calcium, 375-379 parts of perilla seed oil and 28 parts of beeswax by weight, and the phosphorus shrimp oil soft capsule is prepared by the following method: (S1) 28 parts of beeswax are added to 192-200 parts of perilla seed oil, heated to 65-70℃ together, and then cooled to 35-45℃ after the beeswax is melted, 80-90 parts of phosphorus shrimp oil are added and mixed uniformly, and then cooled to 4℃ and left for 2-3h to obtain an oil gel; (S2) 7-10 parts of colostrum basic protein are added to 179-183 parts of perilla seed oil, mixed and stirred for 25min, and then the temperature is lowered to 4℃ and 200 parts of oyster calcium are added, and the mixture is continuously stirred for 20min to obtain a mixture; (S3) the oil gel and the mixture are mixed and stirred, the temperature is slowly raised to 35-45℃ at a rate of 2℃ / min during stirring, and then stirred uniformly, and then sieved through an 80 mesh sieve to obtain the content; (S4) a capsule shell is prepared, the pill is pressed, and the phosphorus shrimp oil soft capsule is obtained.

[0009] The present application adds phosphorus shrimp oil and oyster calcium into perilla seed oil respectively, improves the uniformity of the content, and improves the flowability of the content. Phosphorus shrimp oil is rich in phospholipids, which can reduce the interfacial tension between beeswax and perilla seed oil, improve the dispersion degree of beeswax in perilla seed oil, and form a stable gel network during the standing process after cooling. The addition of oyster calcium to perilla seed oil at 4℃ has the following effects on the uniformity of the content: first, perilla seed oil is in a semi-solid state at a low temperature of 4℃, which has a viscosity control effect, and the increase in the viscosity of perilla seed oil physically prevents the sedimentation of oyster calcium particles therein; second, it has a temperature-phase transition synergistic effect, the saturated fatty acid chains in perilla seed oil form a microcrystalline region, and a dynamic gel network is constructed through hydrogen bonds and van der Waals forces, which can wrap oyster calcium particles to form a steric hindrance effect, preventing oyster calcium from contacting with basic proteins to form a precipitate; third, the rheological characteristics of the content are optimized, and the storage modulus (G') of the semi-solid perilla seed oil is significantly higher than the loss modulus (G'') at low temperature, showing an elastic effect similar to a solid. When mixed with an oil gel, this property can maintain the continuous phase structure of the beeswax gel, avoiding the collapse of the beeswax gel network during the heating process, which leads to the precipitation of beeswax. During the slow heating process after the mixing of the oil gel and the mixture, the stable gel network structure of beeswax is maintained, avoiding the precipitation of beeswax, which ensures the uniform suspension of oyster calcium in the content and improves the flowability of the content.

[0010] The content prepared by the preparation method has uniform quality and good flowability, facilitating the canning of phosphorus shrimp oil soft capsules, and the obtained product has uniform and stable quality and a long shelf life.

[0011] The perilla seed oil in (S1) is 196 parts.

[0012] The weight ratio of perilla seed oil to beeswax in (S1) is 7:1, which can ensure the uniformity of the content and meet the canning efficiency, avoiding the difficulty in pressing pills due to poor flowability.

[0013] In (S2), 10 parts of colostrum basic protein are added to 181 parts of perilla seed oil, mixed and stirred for 25 min, and then the temperature is lowered to 4℃ and 200 parts of oyster calcium are added, and the mixing and stirring is continued for 20 min to obtain a mixture.

[0014] Oyster calcium is heavy and tends to settle after being added to perilla seed oil, and cannot be stably suspended in perilla seed oil. In the present application, the perilla seed oil is cooled to 4℃ to form a semi-solid state, the density difference with oyster calcium is reduced, the settling speed is reduced, and through mixing and stirring, the high viscosity of the low-temperature oil phase can enhance the shearing of oyster calcium particles, promoting uniform dispersion.

[0015] The oyster calcium is slowly added along the container wall, and stirring is carried out while adding; the stirring speed is 200 rpm when the oyster calcium is added, and the stirring speed is 300 rpm after the oyster calcium is added.

[0016] In order to prevent the oyster calcium from mixing a large amount of gas when mixed and stirred with the perilla seed oil, the oyster calcium needs to be slowly added along the container wall, and the stirring speed is low when the oyster calcium is added, so as to avoid excessive shearing and mixing of bubbles; after the oyster calcium is completely added, the stirring speed is increased, so as to fully destroy the oyster calcium agglomerates and improve the uniformity and stability of the contents.

[0017] In step S3, the mixture is stirred after being mixed with the oil gel, and the stirring is slowly heated to 40 DEG C at a rate of 2 DEG C / min; the stirring is carried out at 40 DEG C for 25 min, and the contents are obtained after being screened through an 80-mesh screen.

[0018] In step S3, the stirring speed is 100 rpm.

[0019] The contents include 85 parts of the krill oil, 10 parts of the colostrum basic protein, 200 parts of the oyster powder, 377 parts of the perilla seed oil and 28 parts of the beeswax.

[0020] The capsule skin includes 250 parts of gelatin, 250 parts of purified water, 130 parts of glycerol and 20 parts of titanium dioxide.

[0021] The application has the advantages and positive effects that the preparation method is simple, the cost is low, the contents have good fluidity, the soft capsules are suitable for canning, the prepared krill oil soft capsules are uniform and stable in quality, and have a long shelf life. BRIEF DESCRIPTION OF DRAWINGS

[0022] Figure 1 The content sedimentation ratio in the accelerated stability experiment of experimental example 2 is shown in the ratio line graph.

[0023] Figure 2 The bone density data of mice in experimental example 3 is shown in the columnar graph. DETAILED DESCRIPTION Example 1

[0024] (S1) 196 parts of perilla seed oil were added with 28 parts of beeswax, heated together to 70°C, and after the beeswax was melted, the temperature was lowered to 40°C, 85 parts of phospholipid oil were added and mixed uniformly, and cooled to 4°C for 2 hours to obtain an oil gel; (S2) 10 parts of colostrum basic protein were added to 181 parts of perilla seed oil, mixed and stirred for 25 minutes, and then cooled to 4°C. 200 parts of oyster calcium were slowly added along the wall of the container while stirring, the stirring rate was 200 rpm during the addition, and after the addition was completed, the stirring rate was 300 rpm. After the addition was completed, the mixture was stirred for 20 minutes to obtain a mixture; (S3) the oil gel and the mixture were mixed and stirred, the stirring rate was 100 rpm, and the temperature was slowly raised to 35-45°C at a rate of 2°C / min during stirring. Stir uniformly, pass through an 80-mesh sieve to obtain the content; (S4) prepare the capsule shell, press the pills, and obtain the phospholipid oil soft capsules of Example 1. The capsule shell includes 250 parts of gelatin, 250 parts of purified water, 130 parts of glycerol, and 20 parts of titanium dioxide. The purified water, gelatin, glycerol, and titanium dioxide are mixed, heated to 70°C, stirred and gelatinized, degassed under a vacuum of-0.08 MPa, and sieved through a 120-mesh sieve to obtain a glue solution. Stand still to obtain the capsule shell, and keep it ready for use at 55-65°C. The soft capsule specification is 0.7 g / pill of content. Example 2

[0025] (S1) 192 parts of perilla seed oil were added with 28 parts of beeswax, heated together to 65°C, and after the beeswax was melted, the temperature was lowered to 35°C, 90 parts of phospholipid oil were added and mixed uniformly, and cooled to 4°C for 3 hours to obtain an oil gel. (S2) 7 parts of colostrum basic protein were added to 183 parts of perilla seed oil, mixed and stirred for 25 minutes, and then cooled to 4°C. 200 parts of oyster calcium were slowly added along the wall of the container while stirring, the stirring rate was 200 rpm during the addition, and after the addition was completed, the stirring rate was 300 rpm. After the addition was completed, the mixture was stirred for 20 minutes to obtain a mixture; (S3) the oil gel and the mixture were mixed and stirred, the stirring rate was 100 rpm, and the temperature was slowly raised to 35-45°C at a rate of 2°C / min during stirring. Stir uniformly, pass through an 80-mesh sieve to obtain the content; (S4) prepare the capsule shell, press the pills, and obtain the phospholipid oil soft capsules of Example 2. The soft capsule specification is 0.7 g / pill of content. Comparative Example 1

[0026] (S1) 377 parts of perilla seed oil and 28 parts of beeswax were heated together to 70°C, and after the beeswax was melted, the temperature was lowered to 35°C, 85 parts of phospholipid oil, 10 parts of colostrum basic protein, and 200 parts of oyster powder were added and mixed uniformly to obtain the content; (S2) prepare the capsule shell, press the pills, and obtain the soft capsules of Comparative Example 1. The soft capsule specification is 0.7 g / pill of content. Comparative Example 2

[0027] (S1) 196 parts of perilla seed oil is added with 28 parts of beeswax, heated to 70℃ together, and after the beeswax is melted, the temperature is lowered to 40℃, and 85 parts of euphausioid oil is added and mixed uniformly; (S2) 10 parts of colostrum basic protein is added to 181 parts of perilla seed oil, mixed and stirred for 25 min, 200 parts of oyster calcium is added, and mixed and stirred for 20 min to obtain a mixture; (S3) the oil gel is mixed with the mixture and stirred uniformly, and is passed through an 80-mesh sieve to obtain the content; (S4) a capsule skin is prepared, and the pills are pressed to obtain the euphausioid oil soft capsules. The specification of the soft capsules is 0.7 g / pill of the content. Experimental Example 1: Content uniformity detection

[0028] Ten soft capsules prepared in accordance with Example 1 and Example 2 of the present application and Comparative Example 1 and Comparative Example 2 are taken, and the calcium carbonate content in the content of each soft capsule is determined, and the relative content X of the labeled amount is taken as 100. i The average value X 平均 and the standard deviation S of the calcium carbonate content in the content of each soft capsule are calculated, and the absolute value A of the difference between the labeled amount and the average value is calculated. Wherein, A = |100-X 平均 |; S= . The results are shown in Table 1.

[0029] Table 1: Content uniformity of calcium carbonate in soft capsules.

[0030] Group X 平均 (%)]] A S A + 2.2 S Example 1 99.94 0.06 5.28 10.62 Example 2 100.51 0.51 3.76 8.78 Comparative Example 1 99.43 0.57 11.65 38.37 Comparative Example 2 100.76 0.76 10.06 22.88 As shown in Table 1, A+2.2S<L (L=20.0) in Example 1 and Example 2 of the present application, indicating that the content uniformity of calcium carbonate in Example 1 and Example 2 of the present application meets the requirements. A+2.2S>L in Comparative Example 1, indicating that the content uniformity of calcium carbonate in Comparative Example 1 does not meet the requirements, and the oyster calcium is partially aggregated and precipitated, and the uniformity is poor, which does not meet the uniformity requirements of the soft capsule.

[0031] Experimental Example 2: Accelerated stability experiment One hundred soft capsules of euphausioid oil prepared in accordance with Example 1 and Example 2 of the present application and Comparative Example 1 and Comparative Example 2 are taken at random, and a constant temperature and humidity accelerated stability experiment is performed. The experimental method is as follows: the soft capsules prepared in accordance with Example 1 and Example 2 of the present application and Comparative Example 1 and Comparative Example 2 are placed in a constant temperature and humidity incubator, the temperature in the incubator is maintained at 40±2℃, the relative humidity is 75±5%, and the capsules are stored in the dark for 3 months. The content state and the sedimentation ratio F are observed at 0, 1, 2 and 3 months, respectively. F=(H / H0)×100%, H0 is the initial total height of the content placed in a measuring cylinder, and H is the height of the sedimentation layer after the content is placed in the measuring cylinder for 24 h. The results are shown in Table 2. Figure 1 .

[0032] Figure 1As shown, the contents of the soft capsules prepared in Example 1 and Example 2 of the present application at the 0th month are uniform in color, no stratification or precipitation is observed, the contents have good flowability, and the sedimentation ratio is greater than 0.9, indicating that the oyster calcium has good dispersibility in the perilla seed oil and good suspension effect, and meets the requirements for soft capsule compression and canning. At the 1st, 2nd and 3rd months, no obvious stratification and precipitation are observed in the contents of the soft capsules prepared in Example 1 and Example 2, the sedimentation ratio decreases, but is still greater than 0.9, and the oyster calcium-perilla seed oil suspension system is stable. At the 0th month, the stratification and precipitation of the contents of the soft capsules of Comparative Example 1 and Comparative Example 2 are obviously observed, the sedimentation ratio is less than 0.9, and the requirements for soft capsule compression and canning are not met. At the 1st, 2nd and 3rd months, the sedimentation ratio of the contents of the soft capsules prepared in Comparative Example 1 and Comparative Example 2 decreases significantly, indicating that during the storage process, the oyster calcium, beeswax and perilla seed oil in the contents of the soft capsules are phase-separated, the oyster calcium is precipitated, and the beeswax is crystallized and precipitated, and the shelf life is short.

[0033] The experimental results show that the soft capsules of the phosphorus shrimp oil prepared by the method of the present application have good stability, uniform quality and long shelf life. Experimental Example 3 is helpful to improve bone density

[0034] Experimental animals: 48 weaning mice of about 4 weeks old, weighing about 18-22 grams, of the same gender, 8 mice in each group. After a week of adaptation, the mice were fasted for 12 hours, weighed, randomly grouped according to weight, and caged for feeding. Deionized water was drunk to avoid obtaining calcium from drinking water.

[0035] The contents of the soft capsules of phosphorus shrimp oil prepared in Example 1 of the present application were used as the test sample. Three dose groups were set up, 5 times the recommended human dose was used as the low-dose group L, 10 times the recommended human dose was used as the medium-dose group M, and 50 times the recommended human dose was used as the high-dose group H. Another low-calcium control group (calcium content 150 mg / 100 g of feed) C, a calcium carbonate control group (with the same calcium level as the high-dose group) with the same calcium level as the corresponding dose of the test substance, and a sham operation control group (calcium content 1500 mg / 100 g of feed) were also set up. The test sample dose groups and the calcium carbonate control group were prepared using the low-calcium control group (calcium content 150 mg / 100 g of feed) feed. The test sample was given for 3 months. The test substance was given orally by gavage, and the feed intake of each animal was recorded.

[0036] After the animals were fed for 3 months, they were sacrificed, the right femur was stripped, and the bone density of the midpoint and distal end of the femur was measured using a bone density meter. The results are shown in Table 3, Figure 2 .

[0037] Table 3 Functional evaluation of the present application to improve bone density.

[0038] Group Midshaft femur g / cm 2 ]] femoral distal end g / cm 2 ]]> C (X ± S) 0.504±0.041 0.688±0.034 L (X ± S) 0.588±0.045 0.756±0.047 M (X ± S) 0.584±0.036 0.749±0.044 H (X ± S) 0.579±0.058 0.843±0.021 Calcium carbonate control (X ± S) 0.56±0.026 0.8±0.056 Sham control (X ± S) 0.52±0.049 0.621±0.041 P value (L:C) 0.002 0.005 P value (M:C) 0.001 0.008 P value (H:C) 0.010 0.000 P value (calcium carbonate:C) 0.006 0.000 P value (sham:C) 0.512 0.003 The results are as shown in Table 3, Figure 2As shown, the midpoint bone density and distal femur bone density of the low-dose group, the medium-dose group and the high-dose group of mice are significantly higher than those of the sham operation control group and are not lower than those of the corresponding dose calcium carbonate control group, indicating that the absorption rate of calcium in the phosphorus shrimp oil soft capsules prepared in Example 1 of the present application is not lower than that of the calcium carbonate control group, and it is determined that the phosphorus shrimp oil soft capsules of the present application have the effect of helping to improve bone density.

[0039] The above detailed description of the embodiments of the present application is only a preferred embodiment of the present application and cannot be considered as limiting the scope of the present application. Any equivalent changes and improvements made within the scope of the present application should still belong to the patent coverage of the present application.

Claims

1. A krill oil soft capsule that helps improve bone density, characterized in that: By weight, the contents include 85-90 parts krill oil, 7-10 parts colostrum basic protein, 200 parts oyster calcium, 375-379 parts perilla seed oil, and 28 parts beeswax. The krill oil soft capsules are prepared by the following method: (S1) 28 parts beeswax are added to 192-200 parts perilla seed oil and heated together to 65-70°C. After the beeswax melts, the temperature is lowered to 35-45°C, and 80-90 parts krill oil are added and mixed evenly. The mixture is then cooled to 4°C and allowed to stand for 2-3 hours to obtain an oil gel; (S2) 5-15 parts colostrum basic protein are added to 179-183 parts perilla seed oil and mixed and stirred for 25 minutes. Then, the temperature is lowered to 4°C, 200 parts oyster calcium are added, and the mixture is stirred and stirred for another 20 minutes. (S3) Mix the oleogel with the mixture and stir. During stirring, slowly raise the temperature to 35-45℃ at a rate of 2℃ / min. Stir until uniform and pass through an 80-mesh sieve to obtain the contents. (S4) Prepare capsule shells, compress into pellets, and obtain krill oil soft capsules.

2. The krill oil soft capsule that helps improve bone density according to claim 1, characterized in that: (S1) contains 196 parts of perilla seed oil.

3. A krill oil soft capsule for improving bone density according to claim 2, characterized in that: In step (S2), 10 parts of colostrum basic protein were added to 181 parts of perilla seed oil and mixed for 25 minutes. Then, the temperature was lowered to 4°C and 200 parts of oyster calcium were added. The mixture was then stirred for another 20 minutes to obtain the final mixture.

4. A krill oil soft capsule for improving bone density according to claim 3, characterized in that: (S2) Oyster calcium is slowly added along the container wall while stirring. The stirring speed is 200 rpm when adding and 300 rpm after adding.

5. A krill oil soft capsule for improving bone density according to claim 4, characterized in that: (S3) After the oleogel is mixed with the mixture, it is stirred. During the stirring process, the temperature is slowly increased to 40°C at a rate of 2°C / min. The mixture is stirred at 40°C for 25 min and then passed through an 80-mesh sieve to obtain the contents.

6. A krill oil soft capsule for improving bone density according to claim 5, characterized in that: The stirring speed in (S3) is 100 rpm.

7. A krill oil soft capsule for improving bone density according to claim 6, characterized in that: The contents include 85 parts krill oil, 10 parts colostrum basic protein, 200 parts oyster powder, 377 parts perilla seed oil, and 28 parts beeswax.

8. A krill oil soft capsule for improving bone density according to claim 7, characterized in that: The capsule shell consists of 250 parts gelatin, 250 parts purified water, 130 parts glycerin, and 20 parts titanium dioxide.

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