Iron supplement carrier easy to absorb and capable of reducing inflammation as well as preparation and application of iron supplement carrier

Abstract

The invention discloses an easy-to-absorb iron-supplementing carrier capable of reducing inflammation and preparation and application thereof.The iron-supplementing carrier is prepared by packaging a self-prepared citrus polysaccharide iron compound into sodium alginate / chitosan hydrogel pellets, and experiments prove that the iron-supplementing carrier is successfully positioned and released, the content of RBC and HGB in blood is remarkably increased, and the effect of reducing inflammation is achieved. The recovery of iron-deficiency anemia is effectively promoted; meanwhile, it is found that the content of a proinflammatory factor TNF-alpha in serum is reduced, the content of an anti-inflammatory factor IL-10 is remarkably increased, and the occurrence of inflammation is effectively reduced.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of pharmaceuticals and health foods, and particularly relates to an iron supplement carrier which is easy to absorb and can reduce the occurrence of inflammation, and preparation and application thereof. BACKGROUND

[0002] Polyferic iron complex as a new oral iron supplement has attracted attention due to its good water solubility and low side effects, and the nontoxic property of polyferic iron complex at high concentrations also indicates its great potential as an iron supplement. However, polyferic iron complex is easily destroyed in strongly acidic gastric juice, leading to premature release of iron ions and formation of insoluble iron compounds, reducing its effectiveness. The main drawback of this polysaccharide-based carrier is that it cannot safely deliver iron ions to the intestinal absorption site.

[0003] In order to solve the drawbacks of polyferic iron, biodegradable, biocompatible and safe-to-use polymer nanoparticles have been used to deliver hydrophobic bioactive compounds. Iron-containing micro / nanoparticles can be used to circumvent some of the drawbacks of food supplements and iron-fortified food supplements. By loading iron through micro / nanocarriers, the purposes of protection, efficient delivery and efficient absorption are achieved.

[0004] However, the existing micro / nanocarriers have different degrees of problems such as low loading capacity, inability to be efficiently absorbed or causing inflammation in the gastrointestinal tract. SUMMARY

[0005] The present application provides an iron supplement carrier which is easy to absorb and can reduce the occurrence of inflammation, and preparation and application thereof. On the one hand, the iron supplement carrier can be used as an intestinal targeted release system for polyferic iron, maintaining a high iron element for efficient absorption and utilization, and significantly improving the anemia of rats; on the other hand, the iron supplement carrier can effectively inhibit the non-specific release of iron elements, reduce the strong stimulation of traditional iron supplement preparations on the stomach and intestines, reduce the content of pro-inflammatory factor TNF-α in serum, and also significantly increase the content of anti-inflammatory factor IL-10 in serum, and the combination of the two can significantly reduce the occurrence of inflammation.

[0006] Sodium alginate is a biodegradable natural anionic polymer derived from marine brown algae. It has been approved by the US Food and Drug Administration for human use. Sodium alginate can be cross-linked with divalent cations (such as Ca 2+ ) or cationic polymers to form sodium alginate, which is used for active substance encapsulation and oral ingestion, because it has been fully proven to be biodegradable, biocompatible, safe and stable in the gastrointestinal environment. Sodium alginate exhibits high stability in acidic environments (such as the stomach), but it swells and gradually dissolves in alkaline environments (such as the small intestine). The amino groups on chitosan are mainly protonated (-NH 3+), and deprotonated (-NH2) under neutral and alkaline conditions. It can interact electrostatically with mucin on the intestinal mucosa, open the tight junctions between the intestinal mucosal epithelial cells, prolong the residence time of the drug, increase the paracellular permeation of the drug, and thus improve the intestinal absorption of the drug.

[0007] Therefore, coating sodium alginate with chitosan is expected to overcome these problems and enhance the effective release and bioavailability of iron. The pH sensitivity and intestinal mucosa adhesion specific to sodium alginate and chitosan are of great significance for constructing a pH-responsive carrier. In particular, the sodium alginate and chitosan complex exhibits significant advantages in stability and controlled release, and is expected to improve the overall efficacy by improving the delivery and release of iron supplements.

[0008] The present application encapsulates the self-prepared citrus polysaccharide iron complex in sodium alginate / chitosan hydrogel beads, and the prepared iron supplement carrier is verified by experiments to not only successfully release in situ, significantly increase the content of RBC and HGB in blood, and effectively promote the recovery of iron deficiency anemia; but also found that it reduces the content of pro-inflammatory factor TNF-α in serum, actively increases the content of anti-inflammatory factor IL-10, and effectively reduces the occurrence of inflammation.

[0009] Based on this, the present application provides a preparation method of an iron supplement carrier which is easy to absorb and can reduce the occurrence of inflammation, comprising:

[0010] (1) taking citrus polysaccharide, sodium citrate and ferric chloride as raw materials, and using ultrasonic-assisted co-heating method to prepare crude citrus polysaccharide iron, and after re-dissolving, dialysis purification and drying, the crude citrus polysaccharide iron is obtained as a powder of pure citrus polysaccharide iron;

[0011] (2) dissolving the pure citrus polysaccharide iron and sodium alginate in ultrapure water to obtain a mixed solution containing pure citrus polysaccharide iron and sodium alginate;

[0012] (3) adding the mixed solution to a calcium chloride solution through needle dripping, and standing until it is solidified and cross-linked to obtain sodium alginate hydrogel beads embedding pure citrus polysaccharide iron;

[0013] (4) immersing the sodium alginate hydrogel beads embedding pure citrus polysaccharide iron in a chitosan acetic acid solution, and after a certain reaction time, obtaining sodium alginate / chitosan hydrogel beads embedding pure citrus polysaccharide iron, i.e. the iron supplement carrier.

[0014] The following also provides several optional modes, but not as an additional limitation to the above general scheme, but only as a further supplement or preference, without technical or logical contradiction, each optional mode can be combined with the above general scheme alone, and can also be combined between multiple optional modes.

[0015] Optionally, in step (1), the ultrasonic-assisted co-heating method comprises:

[0016] The ferric chloride aqueous solution is slowly added into the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate, the mixed system is uniformly mixed and the pH of the mixed system is adjusted to 7-11, then the mixed system is placed in a 40-45℃ water bath and an ultrasonic probe is inserted into the mixed system, and the reaction is carried out under ultrasonic.

[0017] After the reaction is completed, the temperature is cooled to room temperature, the upper layer of deep red brown liquid is taken by centrifugation, and then the precipitate is taken by centrifugation after alcohol precipitation, and the precipitate is washed and dried to obtain the crude citrus polysaccharide iron.

[0018] Further, when preparing the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate, the mass ratio of the citrus polysaccharide to ultrapure water is 0.1-1:100, and the mass ratio of the sodium citrate to ultrapure water is 0.1-1:100; the concentration of the ferric chloride aqueous solution is 1-5 mol / L; and the volume ratio of the ferric chloride aqueous solution to the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate is 1-1.5:100.

[0019] Optionally, the power of the ultrasonic is 100-300 W, and the ultrasonic time is 60-120 min.

[0020] Further, the pH of the mixed system is adjusted to 9; in the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate, the mass ratio of the citrus polysaccharide to ultrapure water is 0.4:100, and the mass ratio of the sodium citrate to ultrapure water is 0.4:100; the concentration of the ferric chloride aqueous solution is 2 mol / L; the volume ratio of the ferric chloride aqueous solution to the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate is 1.2:100; the power of the ultrasonic is 150 W, and the ultrasonic time is 75 min.

[0021] Optionally, in step (2), the concentration of the pure citrus polysaccharide iron in the mixed solution is 2-10 mg / mL, and the concentration of the sodium alginate is 10-20 mg / mL. Further, the concentration of the pure citrus polysaccharide iron in the mixed solution is 2 mg / mL, and the concentration of the sodium alginate is 10 mg / mL.

[0022] Optionally, the preparation process of the mixed solution comprises:

[0023] The pure citrus polysaccharide iron is first added into ultrapure water, and stirred at 25-30℃ and 400-600 rpm / min for 30-60 min, then the sodium alginate is added, and the temperature is increased to 40-45℃, and the stirring is continued at 800-1000 rpm / min for 90-120 min.

[0024] Optionally, in step (3), the needle tube diameter is 0.5 mm; the dropping time is 1-2 drops / s; the dropping height is 3-5 cm; the calcium chloride concentration is 5-15 mg / mL; the stirring speed during dropping is 500-800 rpm / min; and the solidification and cross-linking time is 2-5 h. Further, the calcium chloride concentration is 15 mg / mL; and the solidification time is 3 h.

[0025] Optionally, in step (4), the acetic acid concentration in the chitosan acetic acid solution is 5-10 mg / mL, and the chitosan concentration is 2-10 mg / mL; the stirring speed during reaction is 250-300 rpm / min; and the stirring time is 2-5 h. Further, the chitosan concentration is 2 mg / mL, the acetic acid concentration is 10 mg / mL, and the stirring time is 2 h at room temperature.

[0026] Optionally, the chitosan has a molecular weight of >500,000 Da.

[0027] The application also provides an iron supplement carrier prepared by the preparation method.

[0028] The application also provides an application of the iron supplement carrier in the preparation of a medicine for treating iron deficiency anemia.

[0029] The application also provides an application of the iron supplement carrier in the preparation of a health care product or a functional food for improving iron deficiency anemia.

[0030] In the application, the treatment or improvement of iron deficiency anemia includes increasing the RBC and HGB contents in blood, reducing the TNF-α content in serum, and increasing the IL-10 content in serum.

[0031] Compared with the prior art, the application has the following beneficial effects:

[0032] The iron supplement carrier of the application can be used as a channel-oriented release system for polysaccharide iron: sodium alginate shows high stability in an acidic environment (such as the stomach), but it swells and gradually dissolves in an alkaline environment (such as the small intestine). The amino groups on chitosan are mainly protonated (-NH 3+ ) under acidic conditions (pH < 6.5), but are deprotonated (-NH2) under neutral and alkaline conditions. The amino groups can electrostatically interact with mucin on the intestinal mucosa, open the tight junctions between the intestinal mucosal epithelial cells, prolong the residence time of polysaccharide iron, increase the paracellular permeation of polysaccharide iron, and thus improve the intestinal absorption of polysaccharide iron.

[0033] The iron supplement carrier of the present application significantly increases the content of RBC and HGB in blood, effectively promotes the recovery of iron deficiency anemia; reduces the content of pro-inflammatory factor TNF-α in serum, and also significantly increases the content of anti-inflammatory factor IL-10, effectively reduces the occurrence of inflammation. BRIEF DESCRIPTION OF DRAWINGS

[0034] Figures la-c UCP-Fe(III), UCP-Fe / CSTPP and PAC prepared in Example 1-Example 3, respectively, are morphology images of;

[0035] Figures 2a-b PA1.5% and PA1.5%C hydrogel beads of Example 3 are surface electron microscope images of freeze-dried;

[0036] Figures 3a-c PAC hydrogel beads of Example 3 are freeze-dried, and the morphology image and the microscope images of the surface and cross section are shown;

[0037] Figure 4 UCP-Fe(III), UCP-Fe / CS TPP and PAC prepared in Example 1-Example 3 are loading capacity results images;

[0038] Figure 5 FeSO4, UCP-Fe(III), UCP-Fe / CS TPP and PAC in simulated digestive juice (gastric juice + intestinal juice) are cumulative release results images.

[0039] Figure 6 The preparation flow chart of Example 3 is shown. DETAILED DESCRIPTION

[0040] The technical solutions in the embodiments of the present application will be described clearly and completely below in combination with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0041] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which the present application belongs. The terms used in the specification of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application.

[0042] Example 1

[0043] Take 0.2 g of citrus polysaccharide (CP, purchased from Tokyo Kasei Co., Ltd.) and 0.2 g of sodium citrate, add 50 mL of ultrapure water, and stir in a water bath (600 rpm, 40°C) until completely dissolved. Slowly add 0.6 mL of ferric chloride solution (2 mol / L) to the system, and adjust the pH of the system to 9.0 with NaOH solution (1 mol / L) and HCl solution (1 mol / L). Then place it in a 45°C constant temperature bath and stir (100 rpm). Insert the ultrasonic probe into the center of the solution. Carry out the reaction under ultrasonic power of 150 W for 75 min. After the reaction is completed, cool to room temperature, centrifuge (8000 x g, 10 min, 25°C), take the upper layer of dark red brown liquid, add about 2 times the volume of anhydrous ethanol to the liquid, and then centrifuge (8000 x g, 10 min, 25°C) to obtain the precipitate. Wash the precipitate with anhydrous ethanol for 3 times. Finally, the precipitate is vacuum freeze-dried to obtain the crude citrus polysaccharide iron prepared by ultrasonic-assisted co-thermal method.

[0044] The crude citrus polysaccharide iron is redissolved with ultrapure water (about 10 mg / mL), and the solution and dialysis liquid (ultrapure water) are dialyzed at a ratio of 1:100 to remove unreacted iron ions and other small molecular inorganic salt impurities. The dialysis liquid is replaced at 3h, 5h and 11h respectively. The sample is vacuum freeze-dried after dialysis to obtain the pure citrus polysaccharide iron (UCP-Fe(III)) prepared by ultrasonic-assisted co-thermal method.

[0045] Example 2

[0046] Preparation of chitosan-sodium tripolyphosphate particles loaded with polysaccharide iron (UCP-Fe / CS) by ionotropic gelation method TPP ): 200 mg of chitosan (CS, degree of deacetylation 70%, MW = 1000000) was dissolved in 100 mL of acetic acid solution (1% v / v) and stirred at room temperature for 3 h to completely dissolve. The pH was adjusted to 5. Then the impurities in the chitosan solution were removed by a 0.8 μm microporous membrane to obtain a 2 mg / mL CS solution. A certain amount of UCP-Fe(III) (prepared in Example 1) was dissolved in ultrapure water to obtain a UCP-Fe(III) solution with a final concentration of 2 mg / mL.

[0047] Different volume ratios of UCP-Fe(III) solution and CS solution were mixed and stirred at room temperature for 1 h. Then a certain amount of sodium tripolyphosphate (TPP) solution (2 mg / mL) was slowly added. Then, the mixed solution with a mass ratio of CS:TPP:UCP-Fe(III) = 3:1:3 was placed in a shaking bed (100 rpm, 25°C, 2 h). The formed particles were centrifuged (5000 x g, 25°C, 10 min) and washed with deionized water for three times. The particles obtained by freeze-drying were used to prepare UCP-Fe / CSTPP .

[0048] Example 3

[0049] UCP-Fe(III) prepared in Example 1 was configured into a 2 mg / mL solution with ultrapure water. A certain amount of sodium alginate (SA) was added into the UCP-Fe(III) solution to make its final content in the solution 1.0% (10 mg / mL), and then placed in a constant temperature water bath for stirring (500 rpm, 25°C, 4 h). The mixed solution was sucked into a syringe (0.5 x 20 mm), and dropped into a calcium chloride solution with a concentration of 1.5% (15 mg / mL) at a rate of about 0.5 drops per second from a height of 5 cm, and solidified slowly with stirring (200 rpm, room temperature, 3 h), and the wet hydrogel microspheres (UCP-Fe(III)@SA, PA) were obtained by filtration. Ca 2+ Sodium alginate was cross-linked to form the hydrogel microsphere core. The PA microspheres were collected and washed three times with ultrapure water to remove uncross-linked ions, and the wet hydrogel microspheres were denoted as PA, and the PA after freeze-drying for 48 hours was denoted as PA 1.5％ .

[0050] The wet PA hydrogel microspheres were then immersed in a chitosan acetic acid solution (chitosan concentration 2 mg / mL, acetic acid concentration 10 mg / mL, w / v, pH 5, CS degree of deacetylation 70%, MW = 1000000) and continuously stirred (200 rpm, room temperature, 2 h) to form a protective shell of CS on the surface of the PA hydrogel microspheres. The UCP-Fe(III)-encapsulated sodium alginate / chitosan hydrogel microspheres (UCP-Fe(III)@Alg / CS, i.e. PAC) were collected and rinsed three times with deionized water to remove excess CS solution (PA Figure 6 ), and the final wet sodium alginate / chitosan hydrogel microspheres were denoted as PAC, and the wet PAC hydrogel microspheres were freeze-dried for 48 hours to obtain the freeze-dried hydrogel microspheres, denoted as PA 1.5％ C.

[0051] Figures la-c The morphology of UCP-Fe(III), UCP-Fe / CSTPP and PAC is shown. It can be seen that UCP-Fe(III) Figure la ) and UCP-Fe / CSTPP Figure lb ) have a more obvious yellow color. Since chitosan is a cationic polysaccharide, and UCP-Fe(III) is negatively charged, the negative charge of UCP-Fe(III) neutralizes the positive charge on the surface of CS, causing the particles to aggregate. The PAC hydrogel microspheres prepared in Example 3 Figure lc) were spherical and yellowish white, and the color of the hydrogel beads became more transparent with the addition of sodium alginate, indicating that the 3D network became more and more loose. The newly synthesized hydrogel in the present application was more uniform in small spherical shape and more convenient, which provided a new possibility for the synthesis of polymer hydrogel.

[0052] The determination method of field emission scanning electron microscope (FE-SEM) is as follows:

[0053] A small amount of sample was dispersed on the sample holder with conductive glue, and the sample holder was placed in the ion sputtering instrument. Gold powder was sputtered on the sample at a current of 40 mA for 80 s, and the surface morphology of the sample was observed under the field emission scanning electron microscope at 30 kV.

[0054] The surface morphology of the PAS hydrogel microspheres was further observed by scanning electron microscope (SEM), and the results are shown in Figures 2a-b , PA 1.5％ The surface of the microspheres (UCP-Fe(III)@SA prepared in Example 3 after freeze-drying) was smooth and had a regular wrinkle structure Figure 2a ), while the surface of the PA 1.5％ C microspheres (UCP-Fe(III)@Alg / CS prepared in Example 3 after freeze-drying) appeared to be more rough and the wrinkles were more irregular Figure 2b ). Chitosan is a high molecular substance, and after being loaded on the surface of sodium alginate microspheres, its molecular chain can interact with sodium alginate. This interaction includes hydrogen bonding or electrostatic interaction, thereby causing a change in the surface tension of the microspheres, making the surface more rough. In addition, the addition of chitosan also causes the microspheres to shrink or change structure during the drying process, further increasing the surface roughness. On this basis, chitosan was successfully wrapped on the surface of PA microspheres, and hydrogel microspheres with a shell-core structure were prepared.

[0055] The determination method of optical microscope is as follows:

[0056] A small amount of sample was dispersed on the glass slide with conductive glue, and the surface morphology and cross-section of the sample were observed by optical microscope.

[0057] The morphology Figure 3a ), surface Figure 3b ) and cross-section Figure 3c ) images of the freeze-dried PAC hydrogel beads (freeze-dried hydrogel microspheres PA 1.5％ C prepared in Example 3) were characterized by electron microscope, see Figures 3a-cAs shown in the figure, folds and creases are formed on the surface of the beads, which is attributed to the dehydration shrinkage effect of the hydrogel network during the curing process. With the addition of sodium alginate, the shrinkage rate increases. This phenomenon occurs because the presence of sodium alginate affects the dehydration shrinkage effect. In addition, the surface image is also observed at a magnification of 300x. As seen in the figure, the beads have a dense surface structure without micropores. The dense surface structure indicates that the PAC hydrogel beads prepared in the present application have better protection for the encapsulated bioactive ingredients. It is observed from the cross-sectional image that the PAC beads exhibit a typical honeycomb network structure. The loose and porous structure of the hydrogel beads can provide a large space for the storage of bioactive ingredients.

[0058] The determination method of the iron content is as follows:

[0059] PA 1.5％ After reconstituting with ultrapure water, 3 mL of the sample is crushed and placed in a 25 mL volumetric flask, 1 mL of hydrochloric acid solution (6 mol / L) is added and mixed, and it is placed at room temperature for 20 min to destroy the polysaccharide iron structure and separate the iron element from the polysaccharide. Then, the iron content of the polysaccharide iron is determined by reference to the o-phenanthroline method.

[0060] The iron content of the polysaccharide iron is calculated by the following formula:

[0061] Iron content = ((A-0.00456) x V1 / 7.65952 x V2 x m) x 100%;

[0062] A: absorbance value;

[0063] V1: volume mL of polysaccharide iron after dissolution and constant volume;

[0064] V2: volume mL of polysaccharide iron solution for detection;

[0065] m: mass mg of polysaccharide iron.

[0066] After determination and calculation, the results are shown in Figure 4 , the loading capacity of UCP-Fe(III) is 128.00 mg / g, the loading capacity of UCP-Fe / CS TPP is 91.56 mg / g, and the loading capacity of PAC is 48.32 mg / g.

[0067] The determination method of in vitro simulated digestion is as follows:

[0068] Preparation of simulated gastric juice and simulated intestinal juice: 2.0 g of sodium chloride and 3.2 g of pepsin (≥500 U / mg, Sigma Company, USA) are dissolved in ultrapure water, the pH is adjusted with concentrated hydrochloric acid, and the volume is made to 1000 mL to obtain pH 2.0 simulated gastric juice (SGF);

[0069] Pig bile salt mixture (25.0 g / L, Shanghai Maikelin Biochemical Science and Technology Co., Ltd.) and pancreas extract (4.0 g / L, Sigma, USA) were each 5.0 mL dissolved in 100 mL NaHCO3(0.1 mol / L) solution, and then diluted to 1000 mL to obtain simulated intestinal fluid (SIF) with pH 7.4.

[0070] First, 10 mL of sample solution (2 mg / mL, PA 1.5％ C was dissolved in 100 mL of super-pure water) was mixed with 50 mL of simulated gastric fluid, respectively, and placed in a constant temperature bath pot for shaking (37°C, 100 rpm, 2 h). Every 20 min, the sample was collected for further analysis, and an equal volume of simulated gastric fluid was supplemented. After 2 h, 25 mL of the mixed solution was taken out and mixed with simulated intestinal fluid at a ratio of 1:1 (v / v), and then the pH of the solution was adjusted to 7.4. The shaking was continued in the constant temperature bath pot (37°C, 100 rpm, 4 h). Every 20 min, 1 mL of sample was taken for further analysis, and an equal volume of simulated intestinal fluid was supplemented. The mixed solution was filtered with a 0.45 μm filter membrane, and the amount of iron ion release was determined by the o-phenanthroline method.

[0071] Figure 5 To determine the cumulative release of FeSO4, UCP-Fe(III), UCP-Fe / CS TPP and PAC in simulated digestive fluid (gastric fluid + intestinal fluid), as shown in Figure 5 Table 2, the amount of polysaccharide iron released from the hydrogel was low after 2 h of incubation in SGF. This is because the hydrogel beads with a high content of sodium alginate have a dense network structure, which limits the diffusion of polysaccharide iron, resulting in a large amount of polysaccharide iron release in the hydrogel with a low content of sodium alginate. When the positively charged -NH 3+ groups are completely deprotonated to -NH2 groups under acidic conditions, they form hydrogen bonds with -OH, which limits the swelling of the microbeads and thus reduces the release of polysaccharide iron. Oral drugs pass through the gastrointestinal tract, and the key site for the absorption of polysaccharide iron is the small intestine. It can be seen that in weakly alkaline media, the increase in the ionization of the carboxyl groups in the PAC beads increases the swelling degree of the hydrogel network, so the amount of polysaccharide iron released under intestinal fluid conditions is significantly increased compared with that released under gastric fluid conditions. The equilibrium is reached after 2 h in the intestinal fluid. The results show that the PAC hydrogel beads can be used as an intestinal directional release system for polysaccharide iron.

[0072] The determination method of the treatment of iron deficiency anemia in vivo is as follows:

[0073] Ten 35-day normal weaned SD female rats were purchased and set as a normal rat group; 40 35-day iron deficiency anemic weaned SD female rats were set as an iron deficiency anemic rat group, a UCP-Fe(III) group, a UCP-Fe / CS TPPand PAC group, 10 rats in each group. On the basis of normal diet, the normal rat group and the iron deficiency anemia rat group orally take 0.2 mL / day of ultrapure water respectively; the UCP-Fe(III), UCP-Fe / CSTPP and PAC groups orally take 0.2 mL / day of corresponding samples respectively (in which the iron content in the sample content is 40 mg / kg). The continuous gavage treatment is carried out for 7 days.

[0074] After the treatment is finished, blood and fresh feces are collected for blood routine and inflammation factor detection respectively. The collected whole blood, serum obtained by centrifugation and fresh feces are characterized by using an animal blood routine detector and an ELISA kit respectively, in which the normal range of the number of red blood cells is 6.32-9.46 x 10 12 / L, the normal range of hemoglobin is 115-143 g / L, and the test results are shown in Table 1.

[0075] Table 1 Oral UCP-Fe(III), UCP-Fe / CSTPP and PAC treatment of iron deficiency anemia rats TPP and PAC group, 10 rats in each group. On the basis of normal diet, the normal rat group and the iron deficiency anemia rat group orally take 0.2 mL / day of ultrapure water respectively; the UCP-Fe(III), UCP-Fe / CSTPP and PAC groups orally take 0.2 mL / day of corresponding samples respectively (in which the iron content in the sample content is 40 mg / kg). The continuous gavage treatment is carried out for 7 days.

[0076]

[0077] It can be known from Table 1 that, compared with UCP-Fe(III) and UCP-Fe / CSTPP, TPP PAC significantly improves the content of RBC and HGB in blood, and effectively promotes the recovery of iron deficiency anemia; UCP-Fe(III) and UCP-Fe / CSTPP TPP Due to premature leakage, the content of pro-inflammatory factor TNF-α in serum is significantly increased, while PAC avoids the increase of the content of pro-inflammatory factor TNF-α caused by premature leakage of iron; in addition, PAC also significantly increases the content of anti-inflammatory factor IL-10, and effectively reduces the occurrence of inflammation.

[0078] The above results show that the PAC hydrogel beads can be used as an intestinal targeted release system of polysaccharide iron, significantly improve the anemia of rats while maintaining a high absorption of iron elements, reduce the stimulation to the intestinal tract, and improve the immunity of rats. Therefore, the application provides a feasible preparation method and application of an iron supplement carrier with high absorption and low side effects.

[0079] The above-described embodiments only express several embodiments of the application, and the description is relatively specific and detailed, but it should not be understood as a limitation on the scope of the patent. It should be pointed out that, for ordinary skilled persons in the art, without departing from the concept of the application, a number of modifications and improvements can be made, which all belong to the protection scope of the application. Therefore, the protection scope of the patent of the application should be subject to the appended claims.

Claims

1. A method for preparing an iron supplement carrier which is easily absorbed and reduces the occurrence of inflammation, characterized in that, The application relates to an iron supplement carrier. The application comprises the following steps: (1) preparing coarse citrus polysaccharide iron by using ultrasonic-assisted co-heating method with citrus polysaccharide, sodium citrate and ferric chloride as raw materials, and then preparing powder-like pure citrus polysaccharide iron by resolubilizing, dialysis purifying and drying the coarse citrus polysaccharide iron; (2) dissolving the pure citrus polysaccharide iron and sodium alginate in ultrapure water to obtain a mixed solution containing the pure citrus polysaccharide iron and sodium alginate; (3) adding the mixed solution to a calcium chloride solution through a needle head, and then allowing the mixed solution to solidify and crosslink to obtain sodium alginate hydrogel beads embedding the pure citrus polysaccharide iron; 2. The production method according to claim 1, characterized by, (4) immersing the sodium alginate hydrogel beads embedding the pure citrus polysaccharide iron in an acetic acid solution of chitosan, and then allowing the sodium alginate hydrogel beads to react with the chitosan for a certain period of time to obtain sodium alginate / chitosan hydrogel beads embedding the pure citrus polysaccharide iron, namely the iron supplement carrier. In step (1), the ultrasonic-assisted co-heating method comprises the following steps: slowly adding a ferric chloride aqueous solution into a mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate, uniformly mixing the mixed solution, adjusting the pH of the mixed system to 7-11, placing the mixed system in a 40-45 DEG C water bath, inserting an ultrasonic probe into the mixed system, and then allowing the mixed system to react under ultrasonic irradiation; 3. The production method according to claim 2, characterized by, cooling the mixed system to room temperature after the reaction is completed, centrifuging the mixed system to obtain a deep red brown liquid, and then performing alcohol precipitation, centrifuging the obtained precipitate, and then washing and drying the precipitate to obtain the coarse citrus polysaccharide iron. When the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate is prepared, the mass ratio of the citrus polysaccharide to ultrapure water is 0.1-1:100, and the mass ratio of the sodium citrate to ultrapure water is 0.1-1:100; the concentration of the ferric chloride aqueous solution is 1-5 mol / L; the volume ratio of the ferric chloride aqueous solution to the mixed aqueous solution dissolving the citrus polysaccharide and sodium citrate is 1-1.5:100; 4. The method of claim 1, wherein, the power of the ultrasonic irradiation is 100-300 W, and the ultrasonic irradiation time is 60-120 min.

5. The preparation method according to claim 1, characterized in that, In step (2), the concentration of the pure citrus polysaccharide iron in the mixed solution is 2-10 mg / mL, and the concentration of the sodium alginate is 10-20 mg / mL.

6. The method of claim 1, wherein, In step (3), the diameter of the needle head is 0.5 mm; the dropping speed is 1-2 drops per second; the dropping height is 3-5 cm; the concentration of the calcium chloride is 5-15 mg / mL; the stirring speed during the dropping process is 500-800 rpm / min; and the solidification and crosslinking time is 2-5 h. In step (4), the concentration of acetic acid in the chitosan acetic acid solution is 5-10 mg / mL, and the concentration of chitosan is 2-10 mg / mL; the stirring speed during the reaction process is 250-300 rpm / min, and the stirring time is 2-5 h.

7. The iron supplement carrier prepared by the preparation method in any one of claims 1-6.

8. The application of the iron supplement carrier in claim 7 in the preparation of a medicine for treating iron deficiency anemia.

10. Use according to claim 8 or 9, characterized in that, 9. The application of the iron supplement carrier in claim 7 in the preparation of a health product or a functional food for improving iron deficiency anemia. The treatment or improvement of iron deficiency anemia includes increasing the RBC and HGB contents in blood, reducing the TNF-alpha content in serum, and increasing the IL-10 content in serum.

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