Formula and preparation method of active folic acid, betaine, B12 and B6 compound special diet

Abstract

The invention discloses an active folic acid, betaine, B12 and B6 compound special diet formula and a preparation method in the field of special diet foods for pregnant women. The formula contains a core compound (310-400 micrograms of active folic acid, 2.5-4 micrograms of vitamin B12 and the like) and a plurality of synergistic components and auxiliary materials necessary for pregnancy according to 10 g per bag or 0.54 g per tablet, and the DHA embedding rate is 90%. The preparation adopts the processes of low-temperature nitrogen protection mixing, low-temperature granulation and the like, so that the retention rate of active ingredients is guaranteed. According to the invention, four types of subdivided formulas are set, the health food is suitable for special crowds in common pregnancy and MTHFR mutation, double-fetal pregnancy and the like, the problems of hyperhomocysteinemia, 25 (OH) D deficiency and the like in pregnancy are specifically improved through multi-mechanism cooperation and low-temperature keep-alive, the intervention cycle is 2-8 weeks, the efficacy is clear, the practicability is strong, and the health food can be widely applied as a special dietary food for pregnant women with complications in pregnancy.

Description

Technical Field

[0001] This invention relates to the field of special dietary foods for pregnant women, specifically to a special dietary formula and preparation method containing active folic acid, betaine, B12, and B6 complex. Background Technology

[0002] Physiological changes during pregnancy lead to a surge in nutritional needs, and single or non-targeted nutritional supplements are insufficient to address multidimensional health issues. Existing technologies have the following key shortcomings: 1) Insufficient targeted treatment for hyperhomocysteinemia (Hcy) Elevated Hcy levels during pregnancy are closely related to MTHFR gene polymorphism: approximately 15% of pregnant women have a homozygous C677T mutation (TT type). Ordinary folic acid (pteroylglutamate) needs to be converted into its active form (5-methyltetrahydrofolate) by the MTHFR enzyme. The enzyme activity of TT type pregnant women is only 30% of that of wild type (CC type), resulting in an improvement rate of only 35-40% for Hcy in TT type pregnant women with ordinary folic acid-specific diets. Most existing active folic acid-specific diets have not optimized vitamin B12 ratios (mostly 1.0g / serving), which cannot provide sufficient methyl donors, resulting in incomplete Hcy metabolic closure. The improvement rate for pregnant women with moderately elevated Hcy (15-20 mol / L) is only 50-55%.

[0003] 2) The mechanism for improving 25(OH)D deficiency is singular. The 25(OH)D deficiency rate during pregnancy reaches 65%. Existing special dietary vitamin D3 supplements are mostly 600 IU / servation, and do not work synergistically with vitamin K2. Although vitamin D3 can promote intestinal calcium absorption, when vitamin K2 is lacking, calcium is easily deposited on the placental blood vessel wall, leading to calcification, which in turn reduces placental blood flow (resistance index RI increases by 10-15%). In addition, pregnant women in the severe 25(OH)D deficiency group (<20 nmol / L) need more than 12 weeks of vitamin D3 supplementation to reach the target (30 nmol / L), which is far beyond the intervention window during pregnancy.

[0004] 3) Insufficient coordination between placental nutrition and amniotic fluid regulation Twin pregnancies have 40% higher placental nutritional requirements than singleton pregnancies. Existing special dietary diets contain 180mg more DHA per serving but do not supplement L-arginine (a key factor in placental vasodilation), resulting in a 25% lower PLGF level in twin placentas compared to singleton pregnancies and a 30% higher incidence of oligohydramnios. At the same time, existing special dietary diets do not address the mechanisms of amniotic fluid production (such as the regulation of AQP8 aquaporin) and only improve amniotic fluid through the logic of water replenishment, with an improvement rate of only 40-45% for oligohydramnios caused by placental insufficiency.

[0005] 4) Low retention rate of active ingredients High-temperature granulation (>50℃) leads to an oxidative degradation rate of 25-30% for DHA and 15-20% for active folic acid. Furthermore, since DHA is not encapsulated in composite wall materials, it is easily deactivated by light, further reducing its efficacy.

[0006] Therefore, those skilled in the art have provided a special dietary formulation and preparation method for an active folic acid-B12 complex to solve the problems mentioned in the background art. Summary of the Invention

[0007] The purpose of this invention is to provide a special dietary formula and preparation method for an active folic acid, betaine, B12, and B6 complex to solve the problems mentioned in the background art.

[0008] To achieve the above objectives, the present invention provides the following technical solution: The active folic acid-B12 complex special dietary formula and preparation method, based on 10g per sachet or 0.54g per tablet, includes the core complex, synergistic ingredients, and excipients. The specific components and content ranges are as follows: Core complex: active folic acid (5-methyltetrahydrofolate calcium) 310ug-400ug, vitamin B12 (methylcobalamin or adenosylcobalamin) 2.5ug-4ug, vitamin B6 (pyridoxine hydrochloride) 2.5mg-3mg, betaine (natural extract) 100mg, wherein the mass ratio of active folic acid to vitamin B12 is 77.5:1-160:1; Synergistic ingredients: Vitamin A 460ug-550ug, Vitamin D3 5.5ug-8ug, Vitamin E 10mg-13mg, Vitamin B2 1.2mg-1.6mg, Zinc 3.5mg-6.5mg, Selenium 26ug-30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug; Excipients: 15-20g maltodextrin, 5-10g whey protein powder, 2-3g fructooligosaccharides, 0.1-0.2g citric acid, 0.01-0.03g steviol glycosides; The mass ratio of maltodextrin to fructooligosaccharides in the excipients is 6:1-8:1; DHA is encapsulated using a maltodextrin-gum arabic composite wall material with an encapsulation rate of 90%.

[0009] As a further technical solution of the present invention, the formula is a basic type (for mild hyperhomocysteinemia), and based on 10g per bag or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with a mass ratio of active folic acid to vitamin B12 of 100:1; the synergistic components are: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.2mg of vitamin B2, 3.5mg of zinc, 26ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K; the excipients include 6g of whey protein powder and 18g of maltodextrin.

[0010] As a further technical solution of the present invention, the formula is an MTHFR mutant adaptor (for pregnant women with homozygous MTHFR C677T mutation), and based on 10g per sachet or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with a mass ratio of active folic acid to vitamin B12 of 100:1; the content of synergistic ingredients is: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.6mg of vitamin B2, 6.5mg of zinc, 30ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K; the excipients include 8g of whey protein powder and 17g of maltodextrin.

[0011] As a further technical solution of the present invention, the formula is for severe 25(OH)D deficiency (for pregnant women with 25(OH)D < 20 nmol / L), based on 10g per bag or 0.54g per tablet, the content of vitamin D3 in the synergistic ingredients is 8ug, and the content of the other synergistic ingredients is: vitamin A 500ug, vitamin E 12mg, vitamin B2 1.5mg, zinc 5mg, selenium 28ug, DHA 150mg, flaxseed oil microcapsule powder 1000mg, calcium 500mg, iron 15mg, niacin 10mg, pantothenic acid 4mg, biotin 40ug, vitamin C 70mg, vitamin B1 1.6mg, vitamin K 50ug; the content of the core complex is: active folic acid 350ug, vitamin B12 3ug, vitamin B6 2.8mg, betaine (naturally extracted) 100mg; the excipients include maltodextrin 17.5g and fructooligosaccharides 2.5g.

[0012] As a further technical solution of the present invention, the formula is for twin pregnancies (targeting the nutritional needs of twin placenta), and based on 10g per bag or 0.54g per tablet, the content of synergistic ingredients is as follows: Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.6mg, Zinc 6.5mg, Selenium 30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic Acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, and the newly added synergistic ingredient L-arginine 0.5-1.0g; the content of the core complex is as follows: Active folic acid 400ug, Vitamin B1 24ug, Vitamin B6 3mg, Betaine (naturally extracted) 100mg; the excipients include whey protein powder 10g and maltodextrin 16g.

[0013] A method for preparing a special dietary formula containing an active folic acid, betaine, B12, and B6 complex includes the following steps: S1: Raw material pretreatment: Active folic acid, betaine, vitamin B12, vitamin B6, vitamin A, vitamin D3, vitamin E, vitamin B2, vitamin K, vitamin C, vitamin B1, niacin, pantothenic acid, biotin, zinc preparation, selenium preparation, iron preparation, and calcium preparation are all passed through an 80-mesh sieve to remove impurities with a particle size >180 μm; DHA is encapsulated using maltodextrin-gum arabic microcapsules at an encapsulation temperature of 30-35℃ and a stirring speed of 800-1000 r / min to obtain DHA microcapsules; flaxseed oil microcapsule powder is pretreated according to conventional processes for later use. S2: Low-temperature mixing: Introduce 99.9% pure nitrogen gas into the twin-helix mixer at a rate of 0.5-1.0 L / min, control the temperature at 25-30℃ and the rotation speed at 150-200 r / min. First, add whey protein powder, maltodextrin, and fructooligosaccharides and mix for 10-12 min. Then, add the core complex and synergistic ingredients except for DHA microcapsules and flaxseed oil microcapsules. Mix for 10 min, then add DHA microcapsules and flaxseed oil microcapsules and continue mixing for 5-8 min until the mixing uniformity is 95%. S3: Granulation and Forming: Add 5% hydroxypropyl methylcellulose ethanol solution (50% ethanol concentration) to the mixed powder as a binder to form a soft material (the soft material can be formed into a ball by hand and easily crumbled by light pinching), granulate through a 16-20 mesh sieve, and dry by forced air at 40-45℃ and a wind speed of 1.5-2.0m / s until the moisture content of the particles is 5%; after drying, granulate through an 18 mesh sieve to remove agglomerated particles (particle size > 1.0mm).

[0014] S4: Finished product packaging: Mix the dried granules with citric acid and steviol glycosides evenly, and package them into aluminum-plastic composite bags (protected from light, oxygen permeability <5cc / 24h) at 10g per bag or 0.54g per tablet, or compress them into tablets (pressure 15-20kN).

[0015] 7. The application of a special dietary formula in the preparation of special dietary foods to improve hyperhomocysteinemia in pregnant women, characterized in that: the special dietary formula is consumed daily in one serving for 2-8 weeks; for the mildly elevated Hcy group (10-15 mol / L), the Hcy reduction is 45%; for the moderately elevated Hcy group (15-20 mol / L), the Hcy reduction is 55%; for the severely elevated Hcy group (>20 mol / L), the Hcy reduction is 60%; and for pregnant women with the MTHFRC677T homozygous mutation, the Hcy improvement rate is 85%.

[0016] 8. The application of special dietary formula in the preparation of special dietary foods that improve 25(OH)D deficiency in pregnant women, nourish the placenta, or optimize amniotic fluid indicators, characterized in that: the special dietary formula is consumed in one serving daily for 2-8 weeks. Improvement of 25(OH)D deficiency: In the group with 25(OH)D < 20 nmol / L, the level increased by 60%; in the group with 25(OH)D 20-30 nmol / L, the level increased by 40%, while the placental blood flow resistance index (RI) decreased by 15%. Nutritional placenta: Placental growth factor (PLGF) levels increased by 50%, superoxide dismutase (SOD) activity in placental tissue increased by 25%, and malondialdehyde (MDA) content decreased by 30%; Optimize amniotic fluid indicators: For the group with low amniotic fluid (AFI 5-8cm), the rate of achieving the target (AFI 8cm) increased by 70%; for the group with insufficient amniotic fluid depth (2-3cm), the proportion of the depth increased to 3cm was 85%.

[0017] Compared with the prior art, the beneficial effects of the present invention are: This invention optimizes the ratio of core complexes and synergistic ingredients through precise design of four sub-categories of formulations, incorporating a variety of essential nutrients for pregnancy, such as vitamins, minerals, DHA, and flaxseed oil. Combined with multi-mechanism synergy and low-temperature preservation technology, it achieves targeted improvement for hyperhomocysteinemia, 25(OH)D deficiency, placental inadequacy, and amniotic fluid abnormalities during pregnancy. It is especially suitable for special populations such as MTHFR mutations and twin pregnancies. It has a high retention rate of active ingredients and a short intervention cycle (2-8 weeks), demonstrating significant creativity and practicality. It can be widely used as a special dietary food for pregnant women with different pregnancy complications. Detailed Implementation

[0018] The technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0019] Special dietary formula Based on 10g per bag or 0.54g per tablet, the product includes the core complex, synergistic ingredients, and excipients. The specific components and their content ranges are as follows: Core complex: active folic acid (5-methyltetrahydrofolate calcium) 310ug-400ug, vitamin B12 (methylcobalamin or adenosylcobalamin) 2.5ug-4ug, vitamin B6 (pyridoxine hydrochloride) 2.5mg-3mg, betaine (natural extract) 100mg, with the mass ratio of active folic acid to vitamin B12 being 77.5:1-160:1.

[0020] Synergistic ingredients: Vitamin A 460ug-550ug, Vitamin D3 5.5ug-8ug (the company's products contain 150IU-1000IU of Vitamin D3, which meets the precise supplementation needs during pregnancy), Vitamin E 10mg-13mg, Vitamin B2 1.2mg-1.6mg, Zinc 3.5mg-6.5mg, Selenium 26ug-30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug.

[0021] Excipients: 15-20g maltodextrin, 5-10g whey protein powder, 2-3g fructooligosaccharides, 0.1-0.2g citric acid, 0.01-0.03g steviol glycosides.

[0022] As a further aspect of the present invention: the formula is a basic type (for mild hyperhomocysteinemia), and based on 10g per sachet or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with a mass ratio of active folic acid to vitamin B12 of 100:1; the synergistic components are: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.2mg of vitamin B2, 3.5mg of zinc, 26ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K; the excipients include 6g of whey protein powder and 18g of maltodextrin.

[0023] As a further embodiment of the present invention: the formula is an MTHFR mutant adaptor (for pregnant women with homozygous MTHFR C677T mutation), and based on 10g per sachet or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with a mass ratio of active folic acid to vitamin B12 of 100:1; the synergistic components are: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.6mg of vitamin B2, 6.5mg of zinc, 30ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K; the excipients include 8g of whey protein powder and 17g of maltodextrin.

[0024] As a further embodiment of the present invention: the formula is for severe 25(OH)D deficiency (for pregnant women with 25(OH)D < 20 nmol / L), based on 10g per bag or 0.54g per tablet, the content of vitamin D3 in the synergistic ingredients is 8ug, and the content of the other synergistic ingredients is: vitamin A 500ug, vitamin E 12mg, vitamin B2 1.5mg, zinc 5mg, selenium 28ug, DHA 150mg, flaxseed oil microcapsule powder 1000mg, calcium 500mg, iron 15mg, niacin 10mg, pantothenic acid 4mg, biotin 40ug, vitamin C 70mg, vitamin B1 1.6mg, vitamin K 50ug; the content of the core complex is: active folic acid 350ug, vitamin B12 3ug, vitamin B6 2.8mg, betaine (naturally extracted) 100mg; the excipients include maltodextrin 17.5g and fructooligosaccharides 2.5g.

[0025] As a further embodiment of the present invention: the formula is for twin pregnancies (targeting the nutritional needs of twin placenta), and based on 10g per bag or 0.54g per tablet, the content of synergistic ingredients is as follows: Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.6mg, Zinc 6.5mg, Selenium 30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic Acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, with the addition of 0.5-1.0g of L-arginine as a synergistic ingredient; the content of the core complex is as follows: Active folic acid 400ug, Vitamin B1 24ug, Vitamin B6 3mg, Betaine (naturally extracted) 100mg; the excipients include 10g of whey protein powder and 16g of maltodextrin.

[0026] As a further embodiment of the present invention: the mass ratio of maltodextrin to fructooligosaccharides in the excipients is 6:1-8:1; DHA is encapsulated using a maltodextrin-gum arabic composite wall material with an encapsulation rate of 90%.

[0027] Preparation method of special dietary formula The application of any of the above-mentioned active folic acid, betaine, B12, and B6 complex dietary formulations includes the following steps: S1: Raw material pretreatment: Active folic acid, betaine, vitamin B12, vitamin B6, vitamin A, vitamin D3, vitamin E, vitamin B2, vitamin K, vitamin C, vitamin B1, niacin, pantothenic acid, biotin, zinc preparation, selenium preparation, iron preparation, and calcium preparation are all passed through an 80-mesh sieve to remove impurities with a particle size >180 μm; DHA is encapsulated using maltodextrin-gum arabic microcapsules at an encapsulation temperature of 30-35℃ and a stirring speed of 800-1000 r / min to obtain DHA microcapsules; flaxseed oil microcapsule powder is pretreated according to conventional processes for later use.

[0028] S2: Low-temperature mixing: Introduce 99.9% pure nitrogen into the double helix mixer, control the temperature at 25-30℃ and the speed at 150-200r / min, first add whey protein powder, maltodextrin, and fructooligosaccharides and mix for 10-12min, then add the core complex and synergistic ingredients except for DHA microcapsules and flaxseed oil microcapsule powder, mix for 10min, then add DHA microcapsules and flaxseed oil microcapsule powder, continue mixing for 5-8min, and achieve a mixing uniformity of 95%.

[0029] S3: Granulation and molding: Add 5% hydroxypropyl methylcellulose ethanol solution (ethanol concentration 50%) to the mixed powder as a binder to form a soft material (the soft material can be formed into a ball by hand and easily crumbled by light pinching), granulate through a 16-20 mesh sieve, and dry by forced air at 40-45℃ and wind speed of 1.5-2.0m / s until the moisture content of the particles is 5%.

[0030] S4: Finished product packaging: Mix the dried granules with citric acid and steviol glycosides evenly, and package them into aluminum-plastic composite bags (protected from light, oxygen permeability <5cc / 24h) at 10g per bag or 0.54g per tablet, or compress them into tablets (pressure 15-20kN).

[0031] As a further embodiment of the present invention: in step S2, the nitrogen gas introduction rate is 0.5-1.0 L / min to avoid oxidation of components such as vitamin D3, DHA, and flaxseed oil; in step S3, after drying, the particles are granulated using an 18-mesh sieve to remove agglomerated particles (particle size > 1.0 mm).

[0032] Application of special dietary formulas The application of any of the above-mentioned special dietary formulas in the preparation of special dietary foods for improving hyperhomocysteinemia in pregnant women is characterized in that: the special dietary formula is consumed daily in one serving for 2-8 weeks: for the mildly elevated Hcy group (10-15 mol / L), the Hcy reduction is 45%; for the moderately elevated Hcy group (15-20 mol / L), the Hcy reduction is 55%; for the severely elevated Hcy group (>20 mol / L), the Hcy reduction is 60%; and for pregnant women with the MTHFRC677T homozygous mutation, the Hcy improvement rate is 85%.

[0033] The application of any of the above-mentioned special dietary formulas in the preparation of special dietary foods that improve 25(OH)D deficiency in pregnant women, nourish the placenta, or optimize amniotic fluid parameters is characterized in that: the special dietary formula is consumed daily in one serving for 2-8 weeks. Improvement of 25(OH)D deficiency: In the group with 25(OH)D < 20 nmol / L, the level increased by 60%; in the group with 25(OH)D 20-30 nmol / L, the level increased by 40%, while the placental blood flow resistance index (RI) decreased by 15%. Nutritional placenta: Placental growth factor (PLGF) levels increased by 50%, superoxide dismutase (SOD) activity in placental tissue increased by 25%, and malondialdehyde (MDA) content decreased by 30%; Optimize amniotic fluid indicators: For the group with low amniotic fluid (AFI 5-8cm), the rate of achieving the target (AFI 8cm) increased by 70%; for the group with insufficient amniotic fluid depth (2-3cm), the proportion of the depth increased to 3cm was 85%.

[0034] Example 1: Basic formulation (for mild Hcy elevation) Formula (10g per sachet): Calcium 5-methyltetrahydrofolate 400ug, Vitamin B12 (methylcobalamin) 4ug, Vitamin B6 (pyridoxine hydrochloride) 3mg, Betaine (natural extract) 100mg, Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.2mg, Zinc 3.5mg, Selenium 26ug, DHA 150mg (maltodextrin-gum arabic 1:2 encapsulation), Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, Whey protein powder 6g, Maltodextrin 18g, Fructooligosaccharides 2.5g, Citric acid 0.15g, Steviosides 0.02g.

[0035] Preparation: Following the above preparation method, the mixing temperature was 28℃, the nitrogen rate was 0.8L / min, and the drying temperature was 42℃. The retention rate of active folic acid was 92.5%, and the retention rate of DHA was 90.3%.

[0036] Directions for use: Take one serving daily, mix with warm water (40℃), and consume with breakfast.

[0037] Example 2: MTHFR mutant adaptor formula (TT type pregnant women) Formula (10g per sachet): Calcium 5-methyltetrahydrofolate 400ug, Vitamin B12 (adenosylcobalamin) 4ug, Vitamin B6 (pyridoxine hydrochloride) 3mg, Betaine (natural extract) 100mg, Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.6mg, Zinc 6.5mg, Selenium 30ug, DHA 150mg (1:2.5 encapsulation), Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, Whey protein powder 8g, Maltodextrin 17g, Fructooligosaccharides 2.5g, Citric acid 0.15g, Steviosides 0.02g.

[0038] Preparation: DHA encapsulation temperature 35℃, stirring speed 1000r / min, mixing temperature 30℃, active folic acid retention rate 91.8%.

[0039] Directions for use: 1 serving per day, divided into two doses (5g each) in the morning and evening, to avoid excessive dosage at a single time.

[0040] Example 3: Formula for Severe 25(OH)D Deficiency Formula (10g per sachet): Calcium 5-methyltetrahydrofolate 350ug, Vitamin B12 (methylcobalamin) 3ug, Vitamin B6 (pyridoxine hydrochloride) 2.8mg, Betaine (natural extract) 100mg, Vitamin A 500ug, Vitamin D 38ug, Vitamin E 12mg, Vitamin B2 1.5mg, Zinc 5mg, Selenium 28ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, Whey protein powder 6g, Maltodextrin 17.5g, Fructooligosaccharides 2.5g, Citric acid 0.15g, Steviosides 0.02g.

[0041] Preparation: Vitamin D3 was added after being premixed with other fat-soluble vitamins to avoid uneven dispersion; the mixing temperature was 29℃, the nitrogen gas rate was 0.9L / min, and the retention rate of active ingredients was 92.0%.

[0042] Directions for use: Take one serving daily with lunch to promote the absorption of fat-soluble vitamins.

[0043] Example 4: Twin Pregnancy Formula Formula (10g per sachet): Calcium 5-methyltetrahydrofolate 400ug, Vitamin B12 (methylcobalamin) 4ug, Vitamin B6 (pyridoxine hydrochloride) 3mg, Betaine (natural extract) 100mg, Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.6mg, Zinc 6.5mg, Selenium 30ug, DHA 150mg (1:2.5 encapsulation), Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, L-arginine 1.0g, Whey protein powder 10g, Maltodextrin 16g, Fructooligosaccharides 2.5g, Citric acid 0.15g, Steviosides 0.02g.

[0044] Preparation: L-arginine was dissolved in the binder and added to improve dispersibility; DHA encapsulation temperature was 34℃, stirring speed was 900r / min, mixing temperature was 27℃, and the retention rate of active ingredients was 91.5%.

[0045] Directions for use: Take one serving daily with dinner to reduce fluctuations in placental blood flow at night.

[0046] Comparative Example 1: Regular Folic Acid-B12 Dietary Supplement (Commercially Available) Formula (10g per sachet): 0.4mg folic acid, 1.0g cyanocobalamin, 1.5mg vitamin B6, 400IU vitamin D3, 100mg DHA, 5g whey protein powder, 20g maltodextrin, and 3g sucrose.

[0047] Preparation: High-temperature granulation (60℃), with 65% retention of active ingredients.

[0048] Comparative Example 2: Special Dietary Recipes Without Betaine and Some Co-operating Components Formula (10g per sachet): 400ug active folic acid, 4ug vitamin B12, 3mg vitamin B6, 8ug vitamin D3, 150mg DHA, 6g whey protein powder, 17.8g maltodextrin.

[0049] Preparation: Same as in Example 1, but without synergistic components such as betaine, vitamin A, and vitamin E.

[0050] Comparative Example 3: Twin Special Dietary Therapy with Low Ratio of Synergistic Components Formula (10g per bag): 400ug active folic acid, 4ug vitamin B12, 3mg vitamin B6, 100mg betaine, 100mg DHA, 10g whey protein powder, 16g maltodextrin, and other synergistic ingredients at 50% of those in Example 4.

[0051] Preparation: Same as in Example 4, but with insufficient content of synergistic components.

[0052] Performance testing I. Test Subjects 320 pregnant women in the second trimester (14-20 weeks) were selected and divided into 8 groups (40 people in each group): Example 1-4 groups, Comparative 1-3 groups, and blank control group (normal diet). There were no significant differences in baseline data (age, gestational age, Hcy, 25(OH)D, PLGF, AFI) among the groups (P>0.05). Among them, 40 pregnant women with MTHFRTT type were assigned to Example 2 group, 40 pregnant women with twins were assigned to Example 4 group, and 40 pregnant women with 25(OH)D<20nmol / L were assigned to Example 3 group.

[0053] II. Test Indicators and Methods Hcy: Cyclic enzymatic method (Roche cobas 8000), detection limit 0.5-50 mol / L; 25(OH)D: Chemiluminescence assay (Abbott i2000), detection limit 3-150 nmol / L; PLGF: ELISA method (R&D Systems), detection limit 5-1000 pg / mL; Placental blood flow: Color Doppler ultrasound (Philips EPIQ7) was used to detect the placental blood flow resistance index (RI). Amniotic fluid parameters: Amniotic fluid index (AFI) and maximum amniotic fluid depth (AFV) measured by ultrasound. Retention rate of active ingredients: The content of active folic acid and DHA was detected by HPLC (Shimadzu LC-2030).

[0054] III. Test Results (8 weeks after intervention) Group Hcy decrease (%) Increase in 25(OH)D (%) PLGF increase (%) The percentage decrease in placental RI AFI compliance rate (%) Active folic acid retention rate (%) Example 1 48.25.3 36.54.1 42.35.8 12.52.1 85.0（34 / 40） 92.5 Example 2 (TT type) 68.54.7 35.83.9 45.65.2 13.21.8 87.5（35 / 40） 91.8 Example 3 (25(OH)D < 20 nmol / L) 46.85.1 62.34.5 52.86.0 18.32.3 90.0（36 / 40） 92.1 Example 4 (Twins) 52.14.8 40.33.7 75.26.1 15.62.0 92.5（37 / 40） 90.5 Comparative Example 1 28.55.1 (TT type 18.24.5) 27.84.3 25.65.2 8.51.5 60.0（24 / 40） 65.3 Comparative Example 2 32.54.9 29.64.2 30.55.4 9.21.7 70.0（28 / 40） 91.7 Comparative Example 3 (Twins) 38.85.0 25.73.8 32.55.3 10.81.6 62.5（25 / 40） 90.8 Blank control group 5.22.3 8.52.1 10.23.5 0 (No change) 45.0（18 / 40） - IV. Results Analysis Hcy Improvement: The reduction in Hcy in Example 2 (TT type) (68.5%) was significantly higher than that in Comparative Example 1 (TT type 18.2%), demonstrating the synergistic effect of the precise ratio of active folic acid, betaine, vitamin B12, and B6; the Hcy improvement rate in Examples 1-4 was all >45%, far exceeding that of the blank control group (5.2%), verifying the methyl cycle activation effect of the core complex.

[0055] 25(OH)D Improvement: Example 3 showed an increase in 25(OH)D (62.3%), with a target achievement rate of 82% after 8 weeks, which is 124% higher than Comparative Example 1 (27.8%), verifying the rapid intervention effect of vitamin D3 combined with other synergistic ingredients in this invention.

[0056] Placental nutrition: In Example 4 (twins), the increase in PLGF (75.2%) was significantly higher than that in Comparative Example 3 (32.5%), demonstrating the synergistic effect of DHA, L-arginine, and various vitamins and minerals on placental angiogenesis; In Example 4, placental SOD activity increased by 28% and MDA decreased by 32%, verifying the protective effect of antioxidant components such as vitamin E.

[0057] Amniotic fluid optimization: The AFI achievement rate of Example 4 (92.5%) was significantly higher than that of Comparative Example 3 (62.5%), proving the regulatory effect of the formula of the present invention on amniotic fluid production; the AFI achievement rate of Example 3 (90%) was higher than that of Comparative Example 2 (70%), verifying the indirect improvement effect of multiple synergistic components on placental function.

[0058] This invention optimizes the ratio of core nutrients and synergistic components through the precise design of four sub-categories of formulas. Combining multi-mechanism synergy with low-temperature preservation technology, it achieves targeted improvement for hyperhomocysteinemia, 25(OH)D deficiency, placental inadequacy, and amniotic fluid abnormalities during pregnancy. It is especially suitable for special populations such as MTHFR mutation and twin pregnancies. It has a high retention rate of active ingredients and a short intervention cycle (2-8 weeks). It has significant inventiveness and practicality and can be widely used as a special dietary food for pregnant women with different pregnancy complications.

[0059] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A special dietary formula containing active folic acid, betaine, B12, and B6 complex, characterized by: Based on 10g per bag or 0.54g per tablet, the product includes the core complex, synergistic ingredients, and excipients. The specific components and their content ranges are as follows: Core complex: active folic acid (5-methyltetrahydrofolate calcium) 310ug-400ug, vitamin B12 (methylcobalamin or adenosylcobalamin) 2.5ug-4ug, vitamin B6 (pyridoxine hydrochloride) 2.5mg-3mg, betaine (natural extract) 100mg, wherein the mass ratio of active folic acid to vitamin B12 is 77.5:1-160:1; Synergistic ingredients: Vitamin A 460ug-550ug, Vitamin D3 5.5ug-8ug, Vitamin E 10mg-13mg, Vitamin B2 1.2mg-1.6mg, Zinc 3.5mg-6.5mg, Selenium 26ug-30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug; Excipients: 15-20g maltodextrin, 5-10g whey protein powder, 2-3g fructooligosaccharides, 0.1-0.2g citric acid, 0.01-0.03g steviol glycosides; The mass ratio of maltodextrin to fructooligosaccharides in the excipients is 6:1-8:1; DHA is encapsulated using a maltodextrin-gum arabic composite wall material with an encapsulation rate of 90%.

2. The special dietary formula containing active folic acid, betaine, B12, and B6 complex according to claim 1, characterized in that: The formula is a basic type (for mild hyperhomocysteinemia), and based on 10g per sachet or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with an active folic acid to vitamin B12 mass ratio of 100:1; the synergistic components are: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.2mg of vitamin B2, 3.5mg of zinc, 26ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K; the excipients include 6g of whey protein powder and 18g of maltodextrin.

3. The special dietary formula containing active folic acid, betaine, B12, and B6 complex according to claim 1, characterized in that: The formula is an MTHFR mutant-adapted type (for pregnant women with the MTHFRRC677T homozygous mutation). Based on 10g per sachet or 0.54g per tablet, the core complex content is: 400ug of active folic acid, 4ug of vitamin B12, 3mg of vitamin B6, and 100mg of betaine (naturally extracted), with an active folic acid to vitamin B12 mass ratio of 100:

1. The synergistic components are: 550ug of vitamin A, 38ug of vitamin D, 13mg of vitamin E, 1.6mg of vitamin B2, 6.5mg of zinc, 30ug of selenium, 150mg of DHA, 1000mg of flaxseed oil microcapsule powder, 500mg of calcium, 15mg of iron, 10mg of niacin, 4mg of pantothenic acid, 40ug of biotin, 70mg of vitamin C, 1.6mg of vitamin B1, and 50ug of vitamin K. The excipients include 8g of whey protein powder and 17g of maltodextrin.

4. The special dietary formula containing active folic acid, betaine, B12, and B6 complex according to claim 1, characterized in that: The formula is for women with severe 25(OH)D deficiency (for pregnant women with 25(OH)D < 20 nmol / L). Based on 10g per sachet or 0.54g per tablet, the synergistic components include: Vitamin D3 (8ug), and the following synergistic components: Vitamin A (500ug), Vitamin E (12mg), Vitamin B2 (1.5mg), Zinc (5mg), Selenium (28ug), DHA (150mg), Flaxseed oil microcapsule powder (1000mg), Calcium (500mg), Iron (15mg), Niacin (10mg), Pantothenic Acid (4mg), Biotin (40ug), Vitamin C (70mg), Vitamin B1 (1.6mg), and Vitamin K (50ug). The core complex contains: Active Folic Acid (350ug), Vitamin B12 (3ug), Vitamin B6 (2.8mg), and Betaine (naturally extracted) (100mg). The excipients include maltodextrin (17.5g) and fructooligosaccharides (2.5g).

5. The special dietary formula containing active folic acid, betaine, B12, and B6 complex according to claim 1, characterized in that: The formula is for twin pregnancies (targeting the nutritional needs of twin placenta), and is based on 10g per sachet or 0.54g per tablet. The synergistic ingredients are: Vitamin A 550ug, Vitamin D 38ug, Vitamin E 13mg, Vitamin B2 1.6mg, Zinc 6.5mg, Selenium 30ug, DHA 150mg, Flaxseed oil microcapsule powder 1000mg, Calcium 500mg, Iron 15mg, Niacin 10mg, Pantothenic Acid 4mg, Biotin 40ug, Vitamin C 70mg, Vitamin B1 1.6mg, Vitamin K 50ug, and the newly added synergistic ingredient L-arginine 0.5-1.0g; the core complex contains: Active folic acid 400ug, Vitamin B1 24ug, Vitamin B6 3mg, Betaine (naturally extracted) 100mg; the excipients include whey protein powder 10g and maltodextrin 16g.

6. A method for preparing a special dietary formula containing an active folic acid, betaine, B12, and B6 complex, applicable to any one of the special dietary formulas described in claims 1-5, characterized in that: Includes the following steps: S1: Raw material pretreatment: Active folic acid, betaine, vitamin B12, vitamin B6, vitamin A, vitamin D3, vitamin E, vitamin B2, vitamin K, vitamin C, vitamin B1, niacin, pantothenic acid, biotin, zinc preparation, selenium preparation, iron preparation, and calcium preparation are all passed through an 80-mesh sieve to remove impurities with a particle size >180 μm; DHA is encapsulated using maltodextrin-gum arabic microcapsules at an encapsulation temperature of 30-35℃ and a stirring speed of 800-1000 r / min to obtain DHA microcapsules; flaxseed oil microcapsule powder is pretreated according to conventional processes for later use. S2: Low-temperature mixing: Introduce 99.9% pure nitrogen gas into the twin-helix mixer at a rate of 0.5-1.0 L / min, control the temperature at 25-30℃ and the rotation speed at 150-200 r / min. First, add whey protein powder, maltodextrin, and fructooligosaccharides and mix for 10-12 min. Then, add the core complex and synergistic ingredients except for DHA microcapsules and flaxseed oil microcapsules. Mix for 10 min, then add DHA microcapsules and flaxseed oil microcapsules and continue mixing for 5-8 min until the mixing uniformity is 95%. S3: Granulation and Forming: Add 5% hydroxypropyl methylcellulose ethanol solution (50% ethanol concentration) to the mixed powder as a binder to form a soft material (the soft material can be formed into a ball by hand and easily crumbled by light pinching), granulate through a 16-20 mesh sieve, and dry by forced air at 40-45℃ and a wind speed of 1.5-2.0m / s until the moisture content of the particles is 5%; after drying, granulate through an 18 mesh sieve to remove agglomerated particles (particle size > 1.0mm). S4: Finished product packaging: Mix the dried granules with citric acid and steviol glycosides evenly, and package them into aluminum-plastic composite bags (protected from light, oxygen permeability <5cc / 24h) at 10g per bag or 0.54g per tablet, or compress them into tablets (pressure 15-20kN).

7. The use of any one of the special dietary formulas according to claims 1-5 in the preparation of a special dietary food for improving hyperhomocysteinemia in pregnant women, characterized in that: The special dietary formula is consumed daily for 2-8 weeks. In the group with mildly elevated Hcy (10-15 mol / L), Hcy decreased by 45%; in the group with moderately elevated Hcy (15-20 mol / L), Hcy decreased by 55%; in the group with severely elevated Hcy (>20 mol / L), Hcy decreased by 60%; and in pregnant women with the MTHFRC677T homozygous mutation, the Hcy improvement rate was 85%.

8. The use of any one of the special dietary formulas described in claims 1-5 in the preparation of special dietary foods that improve 25(OH)D deficiency in pregnant women, nourish the placenta, or optimize amniotic fluid parameters, characterized in that: The special dietary formula is to be consumed daily for 2-8 weeks. Improvement of 25(OH)D deficiency: In the group with 25(OH)D < 20 nmol / L, the level increased by 60%; in the group with 25(OH)D 20-30 nmol / L, the level increased by 40%, while the placental blood flow resistance index (RI) decreased by 15%. Nutritional placenta: Placental growth factor (PLGF) levels increased by 50%, superoxide dismutase (SOD) activity in placental tissue increased by 25%, and malondialdehyde (MDA) content decreased by 30%; Optimize amniotic fluid indicators: For the group with low amniotic fluid (AFI 5-8cm), the rate of achieving the target (AFI 8cm) increased by 70%; for the group with insufficient amniotic fluid depth (2-3cm), the proportion of the depth increased to 3cm was 85%.