CN110604308A - A nutritional composition with analgesic effect - Google Patents

A nutritional composition with analgesic effect Download PDF

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Publication number
CN110604308A
CN110604308A CN201810611431.XA CN201810611431A CN110604308A CN 110604308 A CN110604308 A CN 110604308A CN 201810611431 A CN201810611431 A CN 201810611431A CN 110604308 A CN110604308 A CN 110604308A
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China
Prior art keywords
vitamin
nutritional composition
composition according
essence
control group
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CN201810611431.XA
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Chinese (zh)
Inventor
张磊
于多
徐希平
白洁
田敏卿
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AUSA PHARMED Ltd
BEIJING AOSA MEDICINE RESEARCH CENTRE Co Ltd
Shenzhen Flight Nutrition And Health Co Ltd
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AUSA PHARMED Ltd
BEIJING AOSA MEDICINE RESEARCH CENTRE Co Ltd
Shenzhen Flight Nutrition And Health Co Ltd
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Priority to CN201810611431.XA priority Critical patent/CN110604308A/en
Publication of CN110604308A publication Critical patent/CN110604308A/en
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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/15—Vitamins
    • A23L33/155—Vitamins A or D
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

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  • Life Sciences & Earth Sciences (AREA)
  • Mycology (AREA)
  • Health & Medical Sciences (AREA)
  • Nutrition Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Food Science & Technology (AREA)
  • Polymers & Plastics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

The invention relates to a nutritional composition prepared from 200-800ug folic acid, 5-20ug vitamin B12, 1.5-10ug vitamin D and 20 microgram-100 mg vitamin K and a preparation method thereof, wherein the nutritional composition has the functions of easing pain and improving stress capability. The composition provided by the invention is not limited to be prepared into nutriments or health-care foods, and can also be used for preparing medicines. The invention has the following advantages: the vitamins with related functions are selected, the formula is scientific and reasonable, and the components have the efficacy synergistic effect and the accurate nutritional characteristics aiming at various people with pain and reduced stress capability.

Description

A nutritional composition with analgesic effect
Technical Field
The present invention relates to a nutritional composition, and more particularly, to a nutritional composition having analgesic and stress-increasing abilities, which can be used for health foods or medicines.
Background
The vitamin K comprises vitamin K1 extracted from green plants, vitamin K2 extracted from microorganisms, and artificially synthesized vitamins K3 and K4. Among them, vitamin K1 or K2, which enters the human body with food, has a side chain that can be separated in vivo and converted into MK-4, which is considered to have a different gamma carboxylation from vitamin K-dependent proteins, and thus MK-4 is also called active vitamin K; the synthesis of coagulation factors 7, 9, 10 is dependent on vitamin K. Therefore, vitamin K has a main function of promoting blood coagulation, and once a human body is deficient, the blood coagulation time is prolonged, and spontaneous bleeding and bleeding can occur in severe cases. In contrast, active vitamin K (MK-4) has shown almost negligible sedative, anti-stress effects in animal studies; folic acid belongs to B vitamins, influences the metabolism of homocysteine when folic acid is deficient in a human body, and is easy to cause hyperhomocysteinemia, which is considered to be a cardiovascular risk factor at present and is related to the increase of pain sensitivity; vitamin B12Also called cobalamin, exists in the form of coenzyme, can enhance the utilization rate of folic acid, and in addition, vitamin B12And folic acid also has important function for maintaining the normal function of the central nervous system; vitamin D can improve the absorption of the body to calcium and phosphorus, regulate the concentration of calcium and phosphorus in blood plasma, promote the growth and calcification of bones, and in addition, the supplement of vitamin D can be beneficial to improving the stress capability of the body.
At present, a plurality of vitamin complex products in the market are nutritional supplements which can be taken by various people, but the actual health care effect is unpredictable because of more components, lower content of each element and lack of pertinence. Therefore, the invention aims to develop a nutritional health-care product for assisting analgesia and improving stress capability, which is a significant improvement on the existing multivitamin product and also conforms to the current development trend of accurate nutrition.
Disclosure of Invention
The invention aims to solve the technical problem of providing a nutritional composition capable of easing pain and improving stress capacity, which comprises the following components:
1) 200-;
2)5-20ug vitamin B12;
3)1.5-10ug vitamin D;
4)20 mu g to 100mg of vitamin K;
5) and (5) auxiliary materials.
In the nutritional composition provided by the invention, the preferable content of folic acid is 400-800ug, the preferable content of vitamin B12 is 5-10ug, the preferable content of vitamin D is 5-10ug, the preferable content of vitamin K is 60 mu g-10 mg, and the more preferable content of vitamin K is 80-200 mu g.
In the present invention, the folic acid includes folic acid, 5-methyltetrahydrofolic acid (calcium), leucovorin, folinic acid, calcium levofolinate, etc., i.e., various folic acid forms including artificial synthesis and plant extract sources, and folic acid and 5-methyltetrahydrofolic acid (calcium) are preferred.
In the invention, the B12 comprises cyanocobalamine, mecobalamin, cobamamide and hydroxocobalamine.
In the invention, the vitamin K comprises K1 of plant origin, K2 of microbial origin, and artificially synthesized K3 and K4, preferably K1 of plant origin and K2 of microbial origin.
In the present invention, said vitamin D is preferably vitamin D2 (ergocalciferol) and vitamin D3.
The nutritional composition can be prepared into oral dosage forms such as common tablets, chewable tablets, soft capsules, hard capsules, lipid nanoparticles, powder, granules and the like.
In the invention, the auxiliary materials are selected from one or more of a filling agent, a wetting agent, an adhesive, a disintegrating agent, a lubricant, a flavoring agent, a stabilizing agent, an embedding substance, a coating premixing agent and an edible pigment.
The filler comprises one or more of starch, soluble starch, dextrin, maltodextrin, potato starch, corn starch, wheat starch, D-mannitol, calcium hydrogen phosphate, anhydrous calcium hydrogen phosphate, maltose, xylitol, sorbitol, microcrystalline cellulose, isomaltulose, milk powder, low-substituted hydroxypropyl cellulose, sucrose, glucose, lactose, pregelatinized starch, maltodextrin and the like.
The wetting agent comprises purified water and ethanol, and the adhesive comprises one or more of hydroxypropyl methyl cellulose, povidone, hydroxypropyl cellulose, sodium carboxymethyl cellulose, starch, methyl cellulose, ethyl cellulose, gelatin, polyethylene glycol, pregelatinized starch, sucrose, glucose and the like.
The disintegrating agent comprises one or more of starch, carboxymethyl starch sodium, crospovidone, croscarmellose sodium, low-substituted hydroxypropyl cellulose, sodium bicarbonate, citric acid and the like, and the lubricant comprises one or more of magnesium stearate, stearic acid, talcum powder, silicon dioxide, hydrogenated vegetable oil, polyethylene glycol, sodium dodecyl sulfate, glyceryl behenate, sodium stearyl fumarate and the like.
The flavoring agent comprises one or more of fruit powder, edible essence, high-intensity sweetener, sour agent and the like, wherein the fruit powder comprises one or more of orange powder, lemon powder, cherry powder, apple powder, strawberry powder, kiwi fruit powder, orange powder, seabuckthorn fruit powder, green plum fruit powder, mango fruit powder, mulberry fruit powder, hawthorn fruit powder, watermelon fruit powder, pineapple fruit powder, blueberry fruit powder, honey peach fruit powder, hami melon fruit powder, grape fruit powder, vanilla fruit powder, pomegranate fruit powder, rose fruit powder and the like.
The edible essence comprises one or more of vanilla essence, sweet orange essence, milk essence, apple essence, grape essence, strawberry essence, pineapple essence, honey peach essence, hami melon essence, lemon essence, cherry essence, sweet corn essence, banana essence, grape essence, rose essence, blackcurrant essence, green apple essence, mango essence, green mango essence, orange essence, fragrant orange essence, snow pear essence, strawberry essence, green plum essence, blueberry essence, waxberry essence, grapefruit essence, pineapple essence, guava essence, passion fruit essence, kiwi fruit essence, cherry essence, kiwi fruit essence, watermelon essence, papaya essence, hami melon essence, durian essence, lychee essence, hawthorn essence, olive essence, mulberry essence and the like.
The high-power sweetener comprises sucralose, aspartame, mogroside, neotame and stevioside, the sour agent comprises citric acid, malic acid, lactic acid, tartaric acid and fumaric acid, the edible pigment comprises caramel color, gardenia yellow, curcumin, chlorophyll, capsicum orange, capsanthin, grape skin red, carmine and aluminum lake thereof, sunset yellow and aluminum lake thereof, brilliant blue and aluminum lake thereof, indigo blue and aluminum lake thereof, beet red, natural amaranth, gardenia blue, plant carbon black, iron oxide red, black bean red, quinoline yellow, lycopene, monascus red, yellow iron oxide, cocoa shell color, safflower yellow, monascus yellow and the like.
The stabilizer comprises vitamin E, dibutyl hydroxy toluene (BHT), Butyl Hydroxy Anisol (BHA) and vitamin C, and the embedding substance comprises one or more of beta-cyclodextrin, alpha-cyclodextrin, gamma-cyclodextrin, dextrin, starch, edible modified starch, sucrose, maltodextrin, gum arabic and the like.
The nutritional composition provided by the invention has a remarkable analgesic effect, and is suitable to be used as an analgesic nutritional product or a health food and an auxiliary medicament.
The nutritional composition provided by the invention also has the obvious effect of improving anti-stress response, avoids the disturbance of the immune function of an organism caused by over-strong stress for a long time, protects the cardiovascular system, the digestive system, the blood system and the like in a stress state, and has good protection effect on high-speed and high-tension emotional states caused by unexpected urgency and danger.
The vitamins with synergistic screening function of the nutritional composition provided by the invention are scientifically formulated, so that the efficacy of the product is ensured, the analgesic effect is obviously enhanced and the anti-stress effect is obviously improved by supplementing the optimal dosage of vitamin B12, vitamin D, vitamin K and folic acid. The nutritional composition provided by the invention is also suitable for health-care food, or used as an auxiliary medicament or a component of related medicaments. The effect of the nutritional composition is significantly better than the effect of the individual application of the components. The nutritional composition provided by the invention is suitable for nutrition and daily health care of clinical patients, old people and pregnant women, and is an ideal treatment auxiliary medicine for the old patients and pregnant patients.
The present invention is further described with reference to the following detailed description, which is not intended to be limiting, but rather is intended to cover by the appended claims any and all equivalent variations of the invention that fall within the true scope of the invention.
Detailed Description
Example 1: folic acid vitamin B12 vitamin D vitamin K tablet
The components are as follows: 400ug of folic acid, vitamin B125 ug, vitamin D5ug, vitamin K80mg, 76mg of microcrystalline cellulose, 16mg of croscarmellose sodium, 8mg of magnesium stearate, povidone K3024 mg and 24mg of film coating agent.
400ug folic acid, 5ug vitamin B12, 5ug vitamin D, 80mg vitamin K and 76mg microcrystalline cellulose were mixed to obtain a mixture, and 16mg croscarmellose sodium was added to the mixture to obtain a mixed powder. Adding 24mg of mixed solution of polyvidone K30 and wetting agent (water or ethanol) into the mixed powder, adding 25ml of mixed solution per 100mg of mixed powder, uniformly binding, and sieving with 18 mesh sieve to obtain granule. Drying the wet granules at 60 ℃ for 4 hours, and controlling the mentioned moisture content to be less than or equal to 7%. The dried granules were sieved through a 18 mesh sieve to obtain dried granules. Magnesium stearate was added and mixed for 10 minutes to obtain total mixed granules. Tabletting the total mixed granules to obtain tablets containing folic acid vitamin B12 vitamin D vitamin K.
Example 2: folic acid vitamin B12 vitamin D vitamin K soft capsule
Prescription:
the preparation method comprises the following steps: adding Cera flava into soybean oil, heating at 50 deg.C to dissolve Cera flava, standing to room temperature, and adding vitamin K, 5-methyltetrahydrofolic acid, vitamin B12, and vitamin D into soybean oil to obtain suspension. Preparing gelatin solution from gelatin, purified water, caramel color and p-hydroxybenzoate, making into soft capsule, shaping, washing, and drying.
Example 3: folic acid vitamin B12 vitamin D vitamin K hard capsule
Prescription:
the preparation method comprises the following steps: mixing folic acid and 20% microcrystalline cellulose, sieving, adding vitamin K, vitamin D and vitamin B12, mixing the obtained raw material mixture with the rest microcrystalline cellulose in an equivalent incremental manner, adding lactose and magnesium stearate, mixing, filling by using a full-automatic capsule filling machine, and polishing to obtain the hard capsule of the pharmaceutical composition.
Example 4: folic acid vitamin B12 vitamin D vitamin K lipid nanoparticle
Preparation: 1. 1.0g of polyethylene glycol-8 caprylocamphetamine, 1.0g of cetearyl glucoside and 92.5g of deionized water were weighed into a beaker and heated in a water bath at 60 ℃.
2. 2.0g of acetylated monoglyceride and 0.5g of caprylic capric glyceride were weighed and heated in a water bath of 60 ℃.
3. Adding folic acid, vitamin B12, vitamin D and vitamin K after the lipid in the beaker is completely melted, and heating and mixing uniformly.
4. Adding the water phase into the system, stirring uniformly, shearing, starting a high-pressure homogenizer, and heating to 60 ℃ by using 70 ℃ deionized water.
5. And injecting the high-temperature emulsion system after being uniformly sheared into a high-pressure homogenizer.
6. Cooling to room temperature to obtain the composite lipid nanoparticles.
EXAMPLE 5 analgesic Effect of Compound composition on mice
30 female mice. Dividing the qualified female mice screened by a hot plate (55.5 +/-0) DEG C pain threshold into 3 groups according to the pain threshold, and 10 mice in each group. The test samples were prepared into a blank control group (equal volume physiological saline), a compound composition group (100mg/kg of the composition preparation shown in example 1) and a vitamin K (80mg/kg) control group, and were injected intraperitoneally for 3 consecutive days, once a day. The effect of the drug on the hot plate pain threshold of the mice was observed 30min and 60min after the last administration.
Female mice were divided into 3 groups of 10 mice each. The test results were divided into a blank control group, a compound composition group (100mg/kg of the composition preparation shown in example 1) and a vitamin K (60mg/kg) control group. Intraperitoneal injection is carried out for 3 consecutive days, once a day. 0.5h after the last administration, each mouse is injected with 10ml/kg of 0.6% acetic acid solution in the abdominal cavity, and then a single mouse is placed in a plastic feeding box, and the time (latency period) for the mouse to generate writhing and the times of writhing within 15min after the injection of acetic acid are observed.
As a result: see tables 1 and 2.
In table 1, compared with the blank control group, the compound composition group and the vitamin K control group did not significantly increase the thermal pain threshold of the mice 30min after administration, but the compound composition group had an upward trend; the compound composition group and the vitamin K control group can obviously improve the thermal pain threshold (P <0.05 or P <0.01) of the mice 60min after the administration. Compared with a vitamin K control group, the compound composition group can obviously improve the hot pain threshold (P <0.05) of the mouse 60min after the administration. The results indicate that the compound composition has more obvious analgesic effect than vitamin K.
In table 2, compared with the blank control group, the writhing latency time of the compound composition group and the vitamin K control group is significantly prolonged (P <0.05 or P <0.01), and the writhing frequency of the mice can be significantly reduced (P <0.01) by the compound composition group. Compared with a vitamin K control group, the compound composition group has longer torsion latency time and fewer torsion times, and shows obvious statistical difference. The results show that the compound composition has obvious analgesic effect which is more obvious than that of vitamin K.
TABLE 1 Effect of Compound composition on Hot plate pain threshold in mice: (n＝10)
Note: compared with the blank control group, the composition of the composition,*P<0.05，**P<0.01; compared with the vitamin K control group,#P<0.05。
TABLE 2 Effect of the combination composition on glacial acetic acid induced writhing response in mice: (n＝10)
Note: compared with the blank control group, the composition of the composition,*P<0.05，**P<0.01; compared with the vitamin K control group,#P<0.05，##P<0.01。
EXAMPLE 6 anti-stress Effect of Compound composition on mice
70 healthy male ICR mice, except for the normal control group, were inoculated with mouse hepatoma H22 ascites tumor strain (1 x 10) aseptically from the right axillary sc6/one), mice were randomized the day after inoculation into 6 groups of 10 mice each: a tumor-bearing control group, a compound composition group (100mg/kg of the composition preparation shown in example 3), a vitamin K control group (200ug/kg), a folic acid control group (800ug/kg), a vitamin B12 control group (10ug/kg), and a vitamin D control group (10 ug/kg). Intraperitoneal injections were given 1 time per day for 10 consecutive days, and the normal and tumor-bearing control groups were given equal volumes of saline. 1h after the last administration, each mouse group is placed into a 125ml wide-mouth bottle containing 5g of calcium chloride, and the bottle mouth is openedAnd (4) timing after sealing, wherein the time from the sealing of the bottle opening to the stopping of respiration of the mouse is the hypoxia tolerance time of the mouse.
70 healthy male ICR mice, except for the normal control group, were inoculated with mouse hepatoma H22 ascites tumor strain (1 x 10) aseptically from the right axillary sc6/one), mice were randomized the day after inoculation into 6 groups of 10 mice each: a tumor-bearing control group, a compound composition group (100mg/kg of the composition preparation shown in example 3), a vitamin K control group (200ug/kg), a folic acid control group (800ug/kg), a vitamin B12 control group (10ug/kg), and a vitamin D control group (10 ug/kg). Intraperitoneal injections were given 1 time per day for 10 consecutive days, and the normal and tumor-bearing control groups were given equal volumes of saline. 0.5h after the last administration, each mouse group was individually placed in water of 20 ℃ with a depth of 30cm, and the time from the time when the mouse was submerged to the time when the mouse stopped breathing was recorded as the swimming time of the mouse.
The results are shown in Table 3.
The hypoxia tolerance time and swimming time of the tumor-bearing mice are obviously shorter than those of a normal control group. The hypoxia tolerance time and the swimming time of the vitamin B12 control group, the vitamin K control group, the vitamin D control group and the folic acid control group have no significant difference with the tumor-bearing control group, and are all obviously lower than those of the normal control group. Although the hypoxia tolerance time and the swimming time of the compound composition group are obviously lower than those of a normal control group, the hypoxia tolerance time and the swimming time are obviously higher than those of a tumor-bearing control group, a vitamin B12 control group, a vitamin K control group, a vitamin D control group and a folic acid control group, and all the statistical differences show that the anti-stress capability of a mouse injected with the compound composition is obviously enhanced, and the compound composition is prompted to have the effect of obviously improving the anti-stress response better than that of a single component.
TABLE 3 Effect of the combination on hypoxia tolerance time and swimming time of tumor-bearing mice: (n＝70)
Note: compared with the normal control group,**P<0.01; compared with the tumor-bearing control group,&P<0.05，&&P<0.01; in comparison to the composite composition set,#P<0.05，##P<0.01。

Claims (10)

1. a nutritional composition comprises
1) 200-;
2)5-20ug vitamin B12;
3)1.5-10ug vitamin D;
4)20ug-100mg vitamin K;
5) and (5) auxiliary materials.
2. Nutritional composition according to claim 1, characterized in that the folic acid comprises folic acid, 5-methyltetrahydrofolic acid, leucovorin, folinic acid, calcium levofolinate.
3. The nutritional composition according to claim 1 wherein B12 comprises cyanocobalamin, methylcobalamin, cyanocobalamin and hydroxycobalamin.
4. Nutritional composition according to claim 1, characterized in that said vitamin K comprises K1 of plant origin, K2 of microbial origin, and artificially synthesized K3 and K4, preferably K1 of plant origin and K2 of microbial origin.
5. The nutritional composition according to claim 1 wherein said vitamin D comprises vitamin D2 and vitamin D3.
6. The nutritional composition according to claim 1, wherein the folic acid content is 400-800ug, the vitamin B12 content is 5-10ug, the vitamin D content is 5-10ug, the vitamin K content is 60 μ g-10 mg, and the preferred vitamin K content is 80-200 μ g.
7. The nutritional composition according to claims 1 to 6, wherein the auxiliary materials are selected from one or more of fillers, wetting agents, binders, disintegrants, lubricants, flavors, food colors, stabilizers, embedding materials, coating premixes, and the like.
8. The nutritional composition according to claims 1-6, characterized in that: the health food is prepared into common tablets, chewable tablets, soft capsules, hard capsules, lipid nanoparticles, powder and granules.
9. Use of the nutritional composition according to claims 1-6 for the preparation of an analgesic preparation.
10. Use of the nutritional composition according to claims 1-6 for the preparation of an anti-stress preparation.
CN201810611431.XA 2018-06-14 2018-06-14 A nutritional composition with analgesic effect Pending CN110604308A (en)

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Cited By (2)

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WO2023275149A1 (en) * 2021-06-29 2023-01-05 Kappa Bioscience As Composition comprising vitamin k, vitamin d
CN115868634A (en) * 2021-09-28 2023-03-31 深圳芙莱特营养与健康有限公司 Composition for enhancing endurance

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023275149A1 (en) * 2021-06-29 2023-01-05 Kappa Bioscience As Composition comprising vitamin k, vitamin d
CN115868634A (en) * 2021-09-28 2023-03-31 深圳芙莱特营养与健康有限公司 Composition for enhancing endurance

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