CN105998059B - A kind of preparation method of albumen iron iron supplementary - Google Patents
A kind of preparation method of albumen iron iron supplementary Download PDFInfo
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- CN105998059B CN105998059B CN201610457867.9A CN201610457867A CN105998059B CN 105998059 B CN105998059 B CN 105998059B CN 201610457867 A CN201610457867 A CN 201610457867A CN 105998059 B CN105998059 B CN 105998059B
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/26—Iron; Compounds thereof
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- A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
- A61K36/815—Lycium (desert-thorn)
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Abstract
The invention discloses a kind of preparation methods of albumen iron iron supplementary, it is to react magnetic nano particle subcarrier with sample solution, makes the transferrins in sample solution in conjunction with the ferric ion on magnetic nano particle subcarrier；Then the magnetic nano particle subcarrier for having adsorbed transferrins is separated with solution with magnet, and by adjust pH make combine transferrins released from magnetic nano particle subcarrier again and and FeCl3Reaction, obtains iron combination transferrins after drying；Iron combination transferrins is mixed with ferrous fumarate, L-AA, blood tonic extract and pharmaceutically acceptable carrier, albumen iron iron supplementary is made.The present invention has many advantages, such as to mend iron effect good, side effect and adverse reaction is few.
Description
Technical field
The invention belongs to hematinic fields, and in particular to a kind of preparation method of albumen iron iron supplementary.
Background technique
Iron ion is microelement necessary to human body, it participates in the synthesis of hemoglobin, is body transport and supply oxygen
The guarantee of gas.Asiderosis is an important factor for causing anaemia, about 50% or more anaemia (i.e. hypoferric anemia, IDA) be due to
Caused by ferro element shortage, and fortification is carried out to asiderosis crowd by iron supplementary, is that preventive and therapeutic action iron lacks
Weary and hypoferric anemia effective measures.
Currently, the type of common iron supplementary has reached tens of kinds, but existing iron supplementary has the shortcomings that: having heavier iron
Fishy smell is not easy to be received by consumer；It is easy to cause gastrointestinal discomfort, user is difficult to adhere to taking for a long time, poor resistance；
The metabolism of part iron supplementary meeting interference medicament.
Transferrins has the active site in conjunction with iron ion, iron ion can be very strongly combined, as iron
Ionophore has significant advantage: can effectively shield iron taste, be easy to be esthetically acceptable to the consumers；After pipe intestinal digesting by
Step release iron ion, plays the role of sustained release, mitigates stimulation of the iron ion to gastrointestinal tract, reduces side effect；Reduce iron ion with
Other drugs avoid the metabolism of interference other medicines in contact in the digestive tract.Therefore, the benefit iron using transferrins as carrier
Agent has the shortcomings that overcome common iron supplementary at present, has significant advantage.
Summary of the invention
The purpose of the invention is to overcome the defect of traditional iron supplementary, provide a kind of without iron taste, GI irritation
It is small, the preparation method of side effect and the albumen iron iron supplementary that adverse reaction is few.
Preparation method provided by the present invention the following steps are included:
(1) with glutaraldehyde as cross linker, magnetic ferric oxide nano grain is reacted with ferric ion, magnetic nano particle is made
Subcarrier；
(2) by after the sample dilution containing transferrins, pH value of solution is adjusted to 6.8-9.5, then by solution weight
Magnetic nano particle subcarrier is added in 0.02-1%, stirs 5-60 minutes, carries transferrins and magnetic nano-particle in solution
Ferric ion on body combines；
(3) with magnet by the magnetic nano-particle carrier adsorption for having adsorbed transferrins to solution bottom, it is molten to discard upper layer
Liquid washs lower layer's solid with the buffer that pH is 6.8-9.5, is then transferred in the buffer that pH is 3.2-4.8, stirs 5-60
Minute, release the transferrins combined from magnetic nano particle subcarrier；Magnetic nano-particle is carried with magnet again
Body and solution separation, FeCl is added into solution3Reaction, obtains iron combination transferrins after drying；
(4) it by iron combination transferrins and ferrous fumarate, L-AA, blood tonic extract and can pharmaceutically connect
The carrier mixing received, is made albumen iron iron supplementary,
The iron combination transferrins, ferrous fumarate, L-AA, blood tonic extract weight ratio be 100:
(0.1-0.5)∶(1-5)∶(5-20)。
The blood tonic extract refers to Chinese medicine with blood nourishing function such as Radix Angelicae Sinensis, Radix Paeoniae Alba, donkey-hide gelatin, jujube, fructus lycii etc.
Water extract or ethanol extract, it is preferable that the blood tonic be one of donkey-hide gelatin, jujube, fructus lycii or a variety of.
Preferably, the sample containing transferrins is egg white or cow's milk.
Beneficial effects of the present invention:
(1) albumen iron iron supplementary prepared by the present invention is made of Multiple components, mutually coordinated between each ingredient, can not or
It lacks, mends iron effect and be substantially better than common iron supplementary, and side effect and less adverse effect, use are safer.
(2) present invention makes iron ion combine closely with transferrins by the preparation method of improvement iron combination transferrins,
It is not easy to release in the gastrointestinal tract, to effectively shield iron taste, alleviates stimulation of the iron ion to gastrointestinal tract, reduce
Side effect and adverse reaction.
(3) present invention improves the purity of iron combination transferrins, reduces the iron ion of impurity and other bonding states,
To further reduced side effect and adverse reaction.
(3) operation of the present invention is simple, with short production cycle, product yield high, while the principle that physical absorption is utilized carries out
Purifies and separates reduce the use of organic reagent as far as possible, not only reduce cost, and more safe and environment-friendly.
Specific embodiment
The present invention is described in detail by the following examples.
Embodiment 1
(1) it is pressed commercially available by the magnetic ferric oxide nano grain (average grain diameter is less than 100nm) of matrix of ferroso-ferric oxide
The ratio of 0.3g/mL is scattered in the phosphate buffer that pH is 8, and 2.5% glutaraldehyde is then added by the volume of buffer,
It is protected from light stirring 3h, glutaraldehyde and magnetic ferric oxide nano grain is crosslinked, uncrosslinked glutaraldehyde molecules is washed away with distilled water, ultrasound
Wave processing 10s disperses nanoparticle, and ferric ion (FeCl is then added into solution3, 20mmol/L), it is stirred to react 5h,
Distilled water washes away extra iron ion, is prepared into magnetic nano particle subcarrier；
(2) egg white is diluted 8 times, adjusts pH to 8.5, magnetic nano-particle then is added by the 0.5% of solution weight
Carrier stirs 10 minutes, makes the ovotransferrins in solution in conjunction with the ferric ion on magnetic nano particle subcarrier；
(3) with magnet by the magnetic nano-particle carrier adsorption for having adsorbed transferrins to container bottom, it is molten to discard upper layer
Liquid, with pH be 8.5 buffer wash lower layer's solid, remove unadsorbed foreign protein, then by solid be transferred to pH be 4 delay
It in fliud flushing, stirs 45 minutes, releases the transferrins combined from magnetic nano particle subcarrier；Reusing magnet will
Magnetic nano particle subcarrier and solution separation, FeCl is added into solution3(25mmol/L) reaction obtains iron combination after drying
Transferrins；
(4) it takes iron combination transferrins 100g, ferrous fumarate 0.2g, L-AA 2g, donkey-hide gelatin 10g, be mixed, then plus
Enter microcrystalline cellulose 10g, pelletize, tabletting is to get benefit iron plate agent.
Embodiment 2
(1) identical as (1) the step of embodiment 1；
(2) cow's milk is diluted 5 times, adjusts pH value of solution to 6.8, magnetic nano particle then is added by the 0.02% of solution weight
Subcarrier stirs 5 minutes, makes the transferrins in solution in conjunction with the ferric ion on magnetic nano particle subcarrier；
(3) with magnet by the magnetic nano-particle carrier adsorption for having adsorbed transferrins to solution bottom, it is molten to discard upper layer
Liquid washs lower layer's solid with the buffer that pH is 6.8, is then transferred in the buffer that pH is 3.2, stirs 60 minutes, make to tie
The transferrins of conjunction is released from magnetic nano particle subcarrier；Magnetic nano particle subcarrier and solution are divided with magnet again
From FeCl is added into solution3(20mmol/L) reaction, obtains iron combination transferrins after drying；
(4) iron combination transferrins 100g is taken, ferrous fumarate 0.1g, L-AA 1g, Fructus Jujubae extract be (jujube
Water extract is bought by commercially available approach) 20g, Icing Sugar granulation is added after mixing, it is dry to get benefit iron particle agent.
Embodiment 3
(1) identical as (1) the step of embodiment 1；
(2) egg white is diluted 10 times, adjusts pH value of solution to 9.5, magnetic nano particle then is added by the 1% of solution weight
Subcarrier stirs 60 minutes, makes the transferrins in solution in conjunction with the ferric ion on magnetic nano particle subcarrier；
(3) with magnet by the magnetic nano-particle carrier adsorption for having adsorbed transferrins to solution bottom, it is molten to discard upper layer
Liquid washs lower layer's solid with the buffer that pH is 9.5, is then transferred in the buffer that pH is 4.8, stirs 5 minutes, make to combine
Transferrins released from magnetic nano particle subcarrier；Magnetic nano particle subcarrier and solution are divided with magnet again
From FeCl is added into solution3(5mmol/L) reaction, obtains iron combination transferrins after drying；
(4) iron combination transferrins 100g, ferrous fumarate 0.5g, L-AA 5g, Fructus lycii P.E (fructus lycii are taken
The ethyl alcohol and water extract of son, are bought by commercially available approach) 5g；It mixes, starch granulation is added, is filled with capsule to get compound
Iron supplement capsules agent.
Through SDS-PAGE electrophoretic analysis, the product purity and yield of Examples 1 to 3 iron combination transferrins see the table below 1.
The purity and yield of 1 iron combination transferrins of table
| Product purity | Yield | |
| Embodiment 1 | 92% | 80% |
| Embodiment 2 | 87% | 73% |
| Embodiment 3 | 82% | 75% |
Embodiment 4
To verify effect of enriching blood of the invention, we carry out following test:
Female Weanling rat 42,4 week old are in a good state of health, and blood picture is normal, 76.57 ± 9.49g of average weight.
6 rats are randomly selected as Normal group, whole process feeding normal diet drinks tap water；Remaining rat feeds low iron feed 4
Week deionized water is drunk, IDA model is established.Hypoferric anemia is typical low pigment small cell types anaemia, shows as serum blood
The significant decrease of Lactoferrin (Hb) is to model successfully as Hb < 100g/L.Therefore, quiet to all rats progress tail after 4 weeks
Arteries and veins takes blood, measures Hb, the results show that normally group content is 148.75 ± 6.90g/L, and the rat Hb value of IDA model group drops
Down to 100g/L hereinafter, average value is 85.79 ± 4.85g/L, it is possible thereby to determine the success of IDA model construction.
6 are chosen from IDA rat and is only used as negative control group, do not add iron supplementary, it is made to continue iron deficiency；Remaining rat point
It is 4 groups, continues to feed low iron feed, drinks deionized water, but supplement the iron supplementary (in terms of iron ion) of same dose, carry out benefit iron
Agent effect experiment.Continue feeding to the 7th week, then taking blood from jugular vein, measures index of correlation.Each group feeding situation is shown in Table 2.
Table 2 tests each group and feeds situation
Between iron supplementation period, each group rat Hb measurement result is as shown in table 3.
3 iron supplementation period rat Hb measurement result of table
The results show that in addition to Normal group, the serum Hb of other each group rats is respectively less than 100g/L mending iron the 0th day,
Show the success of IDA model foundation；During the experiment, negative control group is due to lasting iron deficiency, serum Hb continuous decrease；Tradition is mended
The rat blood serum Hb content of chalybeate group is increased, but is still below Normal group at the 21st day；3 kinds of benefit iron in the present invention
Agent effect is most obvious, and when mending iron the 10th day, serum Hb content has been restored significantly, and at the 21st day, Hb level was more than or has connect
Nearly Normal group shows that the hypoferric anemia of rat is cured completely.These are the results show that transferrins albumen of the invention
Iron iron supplementary using effect is significantly better than traditional iron supplementary.
Claims (2)
1. a kind of preparation method of albumen iron iron supplementary, it is characterised in that the following steps are included:
(1) with glutaraldehyde as cross linker, magnetic ferric oxide nano grain is reacted with ferric ion, magnetic nano-particle load is made
Body；
(2) by after the sample dilution containing transferrins, pH value of solution is adjusted to 6.8-9.5, then presses the 0.02- of solution weight
1% is added magnetic nano particle subcarrier, stirs 5-60 minutes, makes on the transferrins and magnetic nano particle subcarrier in solution
Ferric ion combines；
(3) the magnetic nano-particle carrier adsorption of transferrins will have been adsorbed to solution bottom with magnet, discard upper solution, use
The buffer that pH is 6.8-9.5 washs lower layer's solid, is then transferred in the buffer that pH is 3.2-4.8, stirs 5-60 minutes,
Release the transferrins combined from magnetic nano particle subcarrier；Again with magnet by magnetic nano particle subcarrier and molten
Liquid separation, FeCl is added into solution3Reaction, obtains iron combination transferrins after drying；
(4) by iron combination transferrins and ferrous fumarate, L-AA, blood tonic extract and pharmaceutically acceptable
Carrier mixing, is made albumen iron iron supplementary,
The iron combination transferrins, ferrous fumarate, L-AA, blood tonic extract weight ratio be 100:
(0.1-0.5):(1-5):(5-20)；
The sample containing transferrins is egg white or cow's milk.
2. the preparation method of albumen iron iron supplementary as described in claim 1, it is characterised in that: the blood tonic be donkey-hide gelatin,
One of jujube, fructus lycii are a variety of.
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