CN1850270A - Ovotransferrin iron supplement agent, and its preparing method and use - Google Patents
Ovotransferrin iron supplement agent, and its preparing method and use Download PDFInfo
- Publication number
- CN1850270A CN1850270A CN 200610012762 CN200610012762A CN1850270A CN 1850270 A CN1850270 A CN 1850270A CN 200610012762 CN200610012762 CN 200610012762 CN 200610012762 A CN200610012762 A CN 200610012762A CN 1850270 A CN1850270 A CN 1850270A
- Authority
- CN
- China
- Prior art keywords
- iron
- supplement agent
- iron supplement
- preparation
- gallus domesticus
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Images
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The present invention relates to an egg iron-ion transferring iron-supplementing preparation. Said iron-supplementing preparation contains the coordination compound formed from egg iron-ion transferring and ferric ion, the mole ratio of egg iron-ion transferring and ferric ion is 1:0.5-2. Said coordination compound has maximum absorption peak at 465 nm. Besides, said invention also provides the preparation method of said iron-supplementing preparation and its concrete steps.
Description
Technical field
The present invention relates to a kind of iron ion transferrin, particularly ovotransferrins, specifically belong to a kind of Ovotransferrin iron supplement agent and its production and application.
Background technology
Iron deficiency anemia (IDA) is modal anemia, has a strong impact on human beings'health.The 9th is iron deficiency in the risk factor that has a strong impact on human health of World Health Organization's issue in 2002.IDA is still the general and serious health problem in countries in the world so far, improves the ferrum nutriture, is that the world also is the public health problem that China presses for solution.
Three phases has been experienced in the development of iron enriched nutrient: be to be the inorganic molysite of representative with the ferrous sulfate, i.e. and first generation hardening agent product.Its side effect such as nausea,vomiting,diarrhea, metal abnormal flavour etc., even incidence rate such as iron poisoning is 10%-15%, even greater than 70%, most patients are difficult to stand.
The second filial generation product that comprises organic acid iron salt such as ferrous lactate, Ferrous gluconate.But this type of drug dependence gastric acid discharges ferrum, so it is relatively poor that the achlorhydria patient absorbs, individuality differs greatly for bioavailability of medicament, ferrous salt character is unstable simultaneously, production or storage are all very difficult, and some material combination in soluble iron chemical compound and the food causes that food colour changes, easily produce abnormal flavour, cause the iron supplement effect still not ideal.
Present more use be chelate part such as EDTA because EDTA can form the iron chelate with higher stability constant.Yet, although ferrum EDTA chelate can successfully be absorbed into blood from intestinal,, high stability has produced and the relevant problem of ferrum EDTA chelate, to such an extent as to the too high body of stability can not be separated ferrum easily from part.And even metal ion and EDTA part can separate, but because EDTA is very strong chelating agen, this material also can cause damage to health.
Based on existing technology, synthetic a kind of than existing inorganic iron chemical compound, have more that the organoiron compound of strong biological activity is very important.And synthetic a kind of Stability Analysis of Structures, part are little or have no side effect to health, simultaneously ferrum are discharged easily, are organized the chemical compound that utilizes with organ, can satisfy vast clinical demand more.
According to Qian Zhongming chief editor " iron metabolism-basis is with clinical " (Science Press 2000), transferrins (Transfeerins) is Fe in the vertebrates body
3+The transporter, by with the combining of cell surface TfR, its ferrum that carries is changed in the cell.Transferrins is a big class genetic correlation, the basic structure iron-binding protein similar with biological function.The serum transferrin (Serotansferrin) of typical case's transferrins as in vertebrates blood plasma, spinal fluid, seminal fluid and birds and mammiferous neuron, existing, the general transferrins (representing) that is called for short with Tf, ovotransferrin (the Ovotransferrin that in fowl egg and reptile egg albumen, exists, represent with OTf, also claim ovotransferrins), and the Lactotransferrin (Loactofeerin represents with LTf) that exists in mammal milk, pancreas liquid, tear and the leukocyte endochylema.
From the metabolism of ferrum, behind the drug oral, from gastrointestinal absorption, but in stomach (batch pH1.6～7) holdup time shorter, so main absorption site is in small intestinal (duodenum pH6.0～6.5, jejunum pH6.5～7).As the iron ion of iron supplement agent release, as Fe
2+Must just can enter blood plasma by cell membrane, be oxidized to Fe
3+With de-iron transferrins (apotransgerrin, be called for short apo-Tf) in conjunction with forming ferrum transferrins (transferrin), like this, be that the Fe (blood plasma ferrum) of carrier is transported to bone marrow respectively and is called ferritin and stores it to make hemoglobin and to combine with apoferritin in the storage ferrum tissues such as liver, spleen, bone with apoTf.The cell that is arranged on the intestinal wall resembles one deck mixed solvent (lipid and protein), and cell membrane also is charged macromole lipoid, and protein and mucopolysaccharide are formed, and they can absorb or repel ion, make ion be difficult for passing through cell membrane.So, according to pharmacology and biochemical viewpoint, Fe
2+And Fe
3+Must at first be that part in the enteric liquid cooperates, generate have suitable stability non-and dissociate form and have the fat-soluble mucosa that just easily sees through and enter blood plasma.After entering blood plasma, Fe
2+And Fe
3+Must be released Fe
2+Under blood pH7.4 condition, be oxidized to Fe
3+, could combine with apoTf, according to this viewpoint, no matter be Fe
2+Or Fe
3+, as long as suitable part is arranged with it in conjunction with the coordination compound that forms quite stable, can effectively prevent or suppress Fe
3+(under intestinal pH condition) polymerization can exchange iron ion smoothly with apoTf again, and agent is that the imagination of the iron ion donor in the iron metabolism is rationally feasible as iron supplement.
Summary of the invention
The object of the present invention is to provide a kind of Ovotransferrin iron supplement agent, this iron supplement agent is not only safe in utilization, effect is obvious, and iron supplement agent preparation method is simple.
The object of the present invention is achieved like this:
A kind of Ovotransferrin iron supplement agent wherein contains the coordination compound that ovotransferrins and ferric ion form, and the mol ratio of ovotransferrins and iron ion is 1 in this coordination compound: 0.5--2, and the best is 1: 2; This coordination compound has maximum absorption band (seeing Fig. 1, Fig. 2) at the 465nm place.
The preparation method of Ovotransferrin iron supplement agent of the present invention comprises the steps:
(1) with avian albumen behind the 10-40MPa homogenizing, with the dilution of 1-6 times of normal saline, evenly stir, remove by filter wherein insoluble matter with filter cloth;
(2) configuration quality is than 0.1%-5% iron salt solutions, at room temperature is titrated in the Ovum Gallus domesticus album solution after the above-mentioned dilution, evenly stirs, and the ovotransferrins in Ovum Gallus domesticus album solution is saturated fully;
(3) after the clarification of question response solution,, obtain first product through dialysis or ultrafiltration;
(4) first product obtains the former powder of iron supplement agent through lyophilization, and preserves at 4-8 ℃ of condition lower seal, prevents the moisture absorption and starvation.
Described avian albumen can be Ovum Gallus domesticus album, Ovum Anas domestica album, goose albumen or Carnis Coturnicis japonicae Ovum Gallus domesticus album.
Described iron salt is trivalent iron salt, can be selected from ferric chloride, iron sulfate or ferric citrate etc.
With the former powder of iron supplement agent among the present invention is main active, can be configured to dosage forms such as tablet, capsule, oral granular formulation with pharmaceutically acceptable adjuvant.The iron supplement agent of the present invention of various dosage forms can prepare by this area conventional method.
The former powder of iron-supplementing preparation of the present invention and with the further various dosage forms of preparation of former powder can be used for preparing the application in treatment or auxiliary treatment asiderosis and other disease medicament relevant with iron deficiency.Use this preparation can satisfy the demand of life entity to ferrum.
Compared with prior art, contain Fe in the iron supplement agent of the present invention
3+With the synthetic protein-iron coordination compound of ovotransferrins; its Stability Analysis of Structures, directly body is replenished ferric iron; have no irritating odor; have the advantages that do not precipitate in animal body and easily absorb; part not only has no side effect to health, and can improve the immunity of body, promotes nucleic acid and proteinic metabolism; reduce the side effect that oxidation causes in the body, the cell injury of body is had protective effect.Iron supplement agent of the present invention can be used for treating asiderosis, but and auxiliary treatment other disease relevant such as iron deficiency anemia etc. with ferrum.
Description of drawings
The ultra-violet absorption spectrum of Fig. 1 Ovotransferrin iron supplement agent, it has maximum absorption band at the 465nm place.
Fig. 2 Fe
3+The curve of titration ovotransferrins, the mol ratio of iron ion and ovotransferrins is 2: 1 in this coordination compound.
The curve of Fig. 3 mass ratio 1% liquor ferri trichloridi titration Ovum Gallus domesticus album solution.
The specific embodiment
Further specify the present invention below in conjunction with embodiment.
The preparation of the former powder of embodiment 1 Ovotransferrin iron supplement agent
Raw material: ferric chloride, Ovum Gallus domesticus album
Preparation method comprises the steps:
(1) with Ovum Gallus domesticus album behind the 30MPa homogenizing, with the dilution of 4 times of normal saline, evenly stir, remove by filter wherein insoluble matter with filter cloth;
(2) configuration quality is than 1% liquor ferri trichloridi, at room temperature the 0.44ml liquor ferri trichloridi is added drop-wise in the Ovum Gallus domesticus album after the above-mentioned dilution of 10ml, evenly stirs, and ovotransferrins can make the saturated (see figure 3) of iron ion;
(3) after the clarification of question response solution,, obtain first product, wherein the content 0.465mg/ml of ferrum with the cellophane dialysis;
(4) first product is put into the freezer dryer drying, makes the former powder of iron supplement agent.
Experiment material: Kunming mouse, 8 ages in week, body weight (20.0 ± 2.0) g, male and female half and half;
The agent of this iron supplement contains the Fe amount and is 3.1mg/ml; Erythrocyte diluting fluid;
Superoxide dismutase (SOD) testing cassete and malonaldehyde (MDA) testing cassete.
Experimental technique: 50 mices are divided into four groups of positive controls (I), positive controls (II), experimental group and negative control group etc. at random, and every group of male and female half-and-half.Carry out subcutaneous injection 2% phenylhydrazine by the metering of 0.04ml/kg body weight, the movable normal nothing of mice is dead, thereby sets up mice anemia model.Divide into groups, gavage method and dosage, see Table 1.Measure mouse red blood cell content behind the injection 2d.After 10 days, detected the activity of mouse liver SOD and serum MDA.Each organizes the variation of These parameters following (see Table 2, table 3):
Table 1, mice group, raise, gavage method and dosage
| Group | Feedstuff | Drinking-water | Gavage medicine | Fe content (mg/ml) | Dosage (ml/ time) | Gavage number of times |
| Positive controls I positive controls II experimental group negative control group | Iron deficiency feedstuff iron deficiency feedstuff iron deficiency feedstuff iron deficiency feedstuff | Distilled water distilled water distilled water distilled water | Ferric ammonium citrate ferrous lactate iron supplement agent distilled water | 0.3 20.0 3.1 0.0 | 0.3 0.3 0.1 0.2 | Once a day |
Table 2, preparation are to the influence of anemia model mice RBC (￣ ± s) * 10
12/ L
| RBC | |||
| Group positive controls I positive controls II experimental group negative control group | Gavage 0d 0.5309 ± 0.2127 0.5575 ± 0.1521 0.3511 ± 0.1691 0.3239 ± 0.1921 | Gavage 5d 1.0060 ± 0.1959 1.1840 ± 0.2231 1.1490 ± 0.2561 0.8390 ± 0.1500 | Gavage 10d 1.3010 ± 0.1631 1.5550 ± 0.2320 1.4020 ± 0.2237 * 1.1000±0.1480 |
Annotate: compare with negative control group
*P＜0.05
Table 3, preparation are to anemia model mice liver SOD, the influence of serum MDA
| Group | SOD U/mgprot | MDA nmol/ml |
| Positive controls I positive controls II experimental group negative control group blank group | 18.2106±2.2178 17.5955±1.4583 29.6870±1.4622 * 16.3649±1.1012 14.1430±1.1047 | 4.4731±2.6129 4.3918±1.6906 4.3453±2.3525 9.9010±4.7874 ** 7.3261±1.3856 |
Annotate: compare with negative control group
*P＜0.05; Compare with the blank group
*P＜0.05
Conclusion:
Preparation to anemia model mice iron supplement after, by detecting RBC, can directly reflect the recovery situation of each group.The difference of the RBC content of the comparative experiments group and the positive, negative control group reflects that experimental group RBC recovery situation is better, and the result shows: iron-supplementing preparation has certain blood tonification effect to iron deficiency anemia.By having detected the activity of mouse liver SOD and serum MDA, the result shows: preparation has the significantly effect of antioxidation and anti peroxidation of lipid, can be used for the treatment of for it is clinical or the auxiliary treatment iron deficiency anemia provides certain foundation.
The preparation of embodiment 3 iron-supplementing preparation oral tablets
Composition of raw materials:
Vitamin B12 0.02～0.05 weight portion
Magnesium stearate 0.08～0.2 weight portion
Microcrystalline Cellulose 0.5～0.6 weight portion
Amylum pregelatinisatum 0.5～0.6 weight portion
Method for making: after the former powder of iron supplement agent, vitamin B12, magnesium stearate, microcrystalline Cellulose and amylum pregelatinisatum fully mixed, add after suitable quantity of water mixes, granulate dry, granulate tabletting.
The preparation of embodiment 4 iron-supplementing preparation oral capsules (being used for the treatment of or the simple property of auxiliary treatment iron deficiency anemia)
Composition of raw materials: the former powder of iron supplement agent
Method for making: with the former powder of iron supplement agent as active ingredient and the further ultrafiltration and concentration of pharmaceutical carrier, pulverize dry, add medically acceptable lubricant, by weight for the former powder of iron supplement agent 0.01～99.9% with contain lubricant 99.9%～0.01% and be prepared from 100% composition with arbitrary proportion, carry out 80 mesh sieve branches, granulate, incapsulate filling behind the uniform mixing, polishing.
The preparation of embodiment 5 iron-supplementing preparation oral liquids
Composition of raw materials: the former powder of iron supplement agent
Method for making:
(1) takes by weighing the former powder of iron supplement agent by concentration volume required and that set, add the 70-90% of water for injection then to pre-dosage volume;
(2) with 5%-30% alkaline solution and 5%-10% acid solution dripping or spray pattern is regulated pH to 7.0-9.0, add the water standardize solution and left standstill 72 hours by the concentration of setting, i.e. 100 milliliters of former powder of iron supplement agent that contain setting value, it is qualified to survey osmotic pressure;
(3) add an amount of correctives and antiseptic, after stirring, filter, under aseptic condition, degerming after filtration is sub-packed in aseptic, clean, the exsiccant glass container, sealing.
The preparation of embodiment 6 iron-supplementing preparation granules
Composition of raw materials: the former powder of iron supplement agent, dextrin, cane sugar powder
Method for making: the former powder of iron supplement agent, dextrin, cane sugar powder are crossed 120 mesh sieves respectively weigh standbyly, get the former powder of iron supplement agent, dextrin, the abundant mix homogeneously of cane sugar powder; Make soft material with distilled water, granulate with 18 order nylon screens, dry below 40 ℃ in temperature, and cross 12 mesh sieves, packed for standby use.
Claims (7)
1, a kind of Ovotransferrin iron supplement agent is characterised in that, wherein contains the coordination compound that ovotransferrins and ferric ion form.
2, iron supplement agent as claimed in claim 1 is characterised in that, the mol ratio of ovotransferrins and iron ion is 1 in the described coordination compound: 0.5-2.
3, the preparation method of iron supplement agent as claimed in claim 1 comprises the steps:
(1) with avian albumen behind the 10-40MPa homogenizing, with the dilution of 1-6 times of normal saline, evenly stir, remove by filter wherein insoluble matter with filter cloth;
(2) configuration quality is than 0.1%-5% iron salt solutions, at room temperature is titrated in the Ovum Gallus domesticus album solution after the above-mentioned dilution, evenly stirs, and the ovotransferrins in Ovum Gallus domesticus album solution is saturated fully;
(3) after the clarification of question response solution,, obtain first product through dialysis or ultrafiltration;
(4) first product obtains the former powder of iron supplement agent through lyophilization, and preserves at 4-8 ℃ of condition lower seal.
4, the preparation method of iron supplement agent as claimed in claim 3 is characterised in that, described avian albumen is Ovum Gallus domesticus album, Ovum Anas domestica album, goose albumen or Carnis Coturnicis japonicae Ovum Gallus domesticus album.
5, the preparation method of iron supplement agent as claimed in claim 3 is characterised in that, described iron salt is ferric chloride, iron sulfate or ferric citrate.
6, the preparation method of iron supplement agent as claimed in claim 3 is characterised in that, the former powder of described iron supplement agent can be configured to tablet, capsule, oral granular formulation dosage form with pharmaceutically acceptable adjuvant.
7, the purposes of iron supplement agent as claimed in claim 1 is characterised in that, the application in preparation treatment or auxiliary treatment asiderosis and other disease medicament relevant with iron deficiency.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610012762 CN1850270A (en) | 2006-05-26 | 2006-05-26 | Ovotransferrin iron supplement agent, and its preparing method and use |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610012762 CN1850270A (en) | 2006-05-26 | 2006-05-26 | Ovotransferrin iron supplement agent, and its preparing method and use |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1850270A true CN1850270A (en) | 2006-10-25 |
Family
ID=37131781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610012762 Pending CN1850270A (en) | 2006-05-26 | 2006-05-26 | Ovotransferrin iron supplement agent, and its preparing method and use |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1850270A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105998059A (en) * | 2016-06-22 | 2016-10-12 | 华中农业大学 | Preparation method of transferrin and Fe combined Fe supplementing agent |
| EP4046649A1 (en) | 2021-02-22 | 2022-08-24 | Bioseutica B.V. | Ovotransferrins for use in the treatment of iron deficiency anaemia |
| CN115777939A (en) * | 2022-12-27 | 2023-03-14 | 南京朗博特动物药业有限公司 | Iron-supplementing oral liquid and preparation method thereof |
-
2006
- 2006-05-26 CN CN 200610012762 patent/CN1850270A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105998059A (en) * | 2016-06-22 | 2016-10-12 | 华中农业大学 | Preparation method of transferrin and Fe combined Fe supplementing agent |
| CN105998059B (en) * | 2016-06-22 | 2018-12-25 | 华中农业大学 | A kind of preparation method of albumen iron iron supplementary |
| EP4046649A1 (en) | 2021-02-22 | 2022-08-24 | Bioseutica B.V. | Ovotransferrins for use in the treatment of iron deficiency anaemia |
| WO2022175509A1 (en) | 2021-02-22 | 2022-08-25 | Bioseutica Bv | Ovotransferrins for use in the treatment of iron deficiency anaemia |
| CN115777939A (en) * | 2022-12-27 | 2023-03-14 | 南京朗博特动物药业有限公司 | Iron-supplementing oral liquid and preparation method thereof |
| CN115777939B (en) * | 2022-12-27 | 2023-11-17 | 南京朗博特动物药业有限公司 | Iron supplementing oral liquid and preparation method thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101129351A (en) | Iron supplement composition, its preparing method and application of the same | |
| CN100418548C (en) | Medicinal composition and use thereof | |
| CN1850270A (en) | Ovotransferrin iron supplement agent, and its preparing method and use | |
| CN107417556A (en) | L aspartase calciums and preparation method thereof | |
| CN110172106A (en) | A kind of peach gum polysaccharide iron and its application | |
| CN111494564B (en) | Preparation method of compound liver-protecting and alcohol-dispelling tablet | |
| CN101797276B (en) | Compound vitamin nanoemulsion | |
| CN1116925A (en) | Cod liver oil emulsion and its preparation | |
| CN1429558A (en) | Mannosan peptide injection and its preparation and use method | |
| CN105267945A (en) | Calcium tablet for children and pregnant women | |
| CN1634058A (en) | Vinorelbine emulsion and its preparing method | |
| CN1317033C (en) | Blood nourishing body building composition and its production method | |
| CN105533699A (en) | Compound for supplementing zinc and vitamin in children as well as preparation method and application thereof | |
| CN101912407A (en) | Weight-reducing and lipid-lowering composition | |
| CN1733070A (en) | Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases and its preparing process | |
| CN1823814A (en) | Nutritive lead discharging oral liquid and its preparation method | |
| CN1859922A (en) | Medicinal composition | |
| CN101708184B (en) | Medicine application of iron liposome | |
| CN104688763A (en) | Lysine-vitamin pharmaceutical composition containing chiral isocompounds and use thereof | |
| CN102276687B (en) | Method for separating golden vinegar polypeptide extracts from golden vinegar and product thereof | |
| CN104887696B (en) | Iron-dextrin and ascorbic compound preparation | |
| CN104645334B (en) | N acetylcysteine activated carbon composites and its preparation method and application | |
| CN100364969C (en) | Water soluble vitamins D2 preparation method | |
| CN1579233A (en) | Calcium-cupplemeuting health food containing stachyose | |
| RU2817151C1 (en) | Enterosorbent composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |