CN108524461B - A kind of complex ferrous sulfate sustained release preparation - Google Patents
A kind of complex ferrous sulfate sustained release preparation Download PDFInfo
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- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
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Abstract
The present invention relates to a kind of complex ferrous sulfate sustained release preparation, which includes slow release layer and release layer, wherein the slow release layer includes ferrous sulfate, sustained-release agent and the first excipient；The release layer includes the folic acid and the second excipient wrapped up with cyclodextrin.Sustained release preparation stability of the invention is good, and iron ion is in enteron aisle slow release, small to gastrointestinal stimulation.
Description
Technical field
The present invention relates to technical field of medicine, and in particular to a kind of complex ferrous sulfate sustained release preparation.
Background technique
Increase of the pregnant woman due to body to nutritional ingredient demand, is easier to anaemia occur.There is investigation to show, China women of child-bearing age
In, anaemia incidence incidence in the non-nursing women of unpregnancy is 35.6%, and incidence is 47.6% in nursing women, pregnant
Incidence is 42.1% in woman, and rural area is higher than city.The generation of general anemia accounts for the overwhelming majority with light moderate, therefore is easier to
It is treated by mending iron, benefit folic acid.Anaemia, which is such as not treated in time, will lead to premature labor, the infant of low-birth weight and foetal death.Iron deficiency and lack
Folic acid is the main reason for causing hypoferric anemia and megaloblastic anemia, therefore the enough iron and folic acid of daily iron supplement can be prevented
Control the generation of pregnant woman anemia.Have been reported that the given birth to child of the women of Supplement of folic acid and iron suffers from acute lymphoblastic during showing pregnancy
The ratio of leukaemia lower than unsupplemented average probability 60%.
Iron is that hemoglobin and myoglobins synthesize indispensable raw material, after supplementing chalybeate to iron-deficient patient, can be added
The synthesis of strong hemoglobin, alleviates Anemia.
Folic acid is the important component of internal metabolism, it participates in methylation reaction and cellular replication, and such as lacking folic acid will
Lead to purine and pyrimidine biosynthesis block, is affected so as to cause DNA synthesis, cell splitting rate slows down, and forms haemocyte
Slow down, leads to megaloblastic anemia.Folic acid deficiency is easier to occur in gravid woman, this is because pregnant middle and later periods uterus is expanded
Greatly, placentation, blood volume increase and fetal tissue's fast-growth, demand of the pregnant woman to folic acid steeply rise.There is investigation to show
Incidence of the folic acid deficiency in pregnancy women is up to 26.6%, especially middle and advanced stage pregnant woman.Northern vegetable and fruit not
Area incidence abundant is higher.It recent studies have shown that folic acid deficiency can lead to other a variety of diseases, such as fetus other than anaemia
Nerve channel hypoplasia, cardiovascular and cerebrovascularinfarction and various cancers, therefore pregnancy period and usually positive Supplement of folic acid has very human body
Big benefit.
Ferrous sulfate is formed into compound with quick-release folic acid in a sustained manner, can not only reduce ferrous ion to gastrointestinal tract
Stimulation reduces its side effect, and since the presence of folic acid can form the slightly sour environment in part, is more advantageous to ferrous ion in vivo
Absorption.To more effectively prevent and treat anaemia caused by women, especially status of iron deficiency in pregnant women and afoliate acid.Such as trade name
Are as follows: the tablet (the quick-release folic acid of every sustained release iron ion and 350mg containing 105mg) of Ferrograd Folic is exactly this product
A kind of mainstream product.
However, folic acid in the product meet water, light, heat can fast decoupled, make this product drug effect and stability by compared with
It is big to influence.
Summary of the invention
In order to overcome the drawbacks of the prior art, the application provides a kind of complex ferrous sulfate sustained release preparation, the sustained release preparation
Stability is good, and iron ion is in enteron aisle slow release, small to gastrointestinal stimulation.
Therefore, it is an object of the present invention to provide a kind of complex ferrous sulfate sustained release preparations.
It is a further object to provide a kind of preparation methods of complex ferrous sulfate sustained release preparation.
On the one hand, the present invention provides a kind of complex ferrous sulfate sustained release preparation, which includes slow release layer and quick-release
Layer, wherein the slow release layer includes ferrous sulfate, sustained-release agent and the first excipient；The release layer includes with cyclodextrin encapsulated
Folic acid and the second excipient.
Preferably, in the slow release layer, the sustained-release agent is hydrophilic gel framework material, is selected from carboxymethyl cellulose
One of element, hydroxyethyl cellulose and hydroxypropyl methyl cellulose are a variety of, and preferably viscosity is 50~50000mpa.s's
Hydroxypropyl methyl cellulose；More preferably viscosity be 100~10000mpa.s hydroxypropyl methyl cellulose, most preferably
The hydroxypropyl methyl cellulose of 100mpa.s.
Preferably, in the slow release layer, first excipient is selected from filler, pigment, adhesive, lubricant and helps
Flow one of agent or a variety of.
Preferably, in first excipient, the filler is selected from starch, dextrin, Icing Sugar, lactose and microcrystalline cellulose
One of element is a variety of, preferably lactose and microcrystalline cellulose.
Preferably, in first excipient, the pigment is to commonly use natural or synthetic edible pigment, preferably red
Edible pigment, more preferably famille rose 60.
Preferably, in first excipient, described adhesive be natural or synthetic medicinal adhesive, preferably PVP,
More preferably PVPk30。
Preferably, in first excipient, the lubricant is stearic acid or its salt, more preferably magnesium stearate.
Preferably, in first excipient, the glidant is selected from one of talcum powder and superfine silica gel powder or more
Kind, preferably superfine silica gel powder, more preferably gas phase superfine silica gel powder.
Preferably, in the slow release layer, the sustained-release agent accounts for the 10%~40% of the sustained release preparation total weight, preferably
15%~25%, more preferably 15-19%.
Preferably, in the slow release layer, the ferrous sulfate accounts for the 10%~30% of the sustained release preparation total weight, excellent
Select 5~15%.
Preferably, in the slow release layer, first excipient accounts for the 5%~50% of the sustained release preparation total weight,
It is preferred that 15%~25%.
Preferably, in the release layer, the cyclodextrin is in alpha-cyclodextrin, beta-cyclodextrin and gamma-cyclodextrin
It is one or more, preferably beta-cyclodextrin, more preferably hydroxypropyl-β-cyclodextrin.
Preferably, in the release layer, second excipient is selected from filler, adhesive, lubricant and glidant
One of or it is a variety of.
Preferably, in second excipient, the filler is lactose or starch.
Preferably, in second excipient, described adhesive is selected from natural or synthetic medicinal adhesive, preferably
PVP, more preferably PVPk30。
Preferably, in second excipient, the lubricant is stearic acid or its salt, more preferably magnesium stearate.
Preferably, in second excipient, the glidant is selected from one of talcum powder and superfine silica gel powder or more
Kind, preferably superfine silica gel powder, more preferably gas phase superfine silica gel powder.
Preferably, described in cyclodextrin encapsulated folic acid in the release layer, the folic acid and the cyclodextrin it
Between mass ratio be 1:50~500, preferably 1:200~400, more preferably 1:250~300.
Preferably, in the release layer, it is described with cyclodextrin encapsulated folic acid the preparation method is as follows:
Folic acid is dissolved in dehydrated alcohol, cyclodextrin is added, is stirred, it is dry；
Preferably, mixing time be 0.5~10 hour, preferably 1~3 hour,
Preferably, drying temperature is 10~80 DEG C, preferably 30~50 DEG C.
In a special specific embodiment, it is described with cyclodextrin encapsulated folic acid the preparation method is as follows:
1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 250g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, mistake
Filter, 50ml ethanol washing, 40 DEG C of vacuum drying.
Preferably, described that the 5% of the sustained release preparation total weight is accounted for cyclodextrin encapsulated folic acid in the release layer
~25%, preferably 10%~20%.
Preferably, in the release layer, second excipient accounts for the 5%~50% of the sustained release preparation total weight,
It is preferred that 10%~30%.
Preferably, the weight ratio between the slow release layer and the release layer is 1~2:1, preferably 1~1.5:1.
In a preferred embodiment, the technical solution of complex ferrous sulfate sustained release preparation of the invention is as follows:
Preparation method:
A, the preparation of dried ferrous sulfate
After medicinal ferrous sulfate (CP2000 standard contains 7 crystallizations water) is crushed with Universalpulverizer, 80 meshes are crossed, in
40-45 DEG C heated-air drying 36-48 hours, crushed, sieved with 100 mesh sieve with Universalpulverizer after cooling, it is qualified after measured (to meet
The BP1988 editions standards in relation to dried ferrous sulfate) it is spare afterwards.
B, it is sustained the preparation of ferrous sulfate particle
Dried ferrous sulfate and lactose, microcrystalline cellulose and HPMCk100First mix spare, carmine 60,30 POVIDONE K 30 BP/USP30With
40% (w/v) ethyl alcohol dissolves, and is added in the above-mentioned mixed powder being pre-mixed, and is routinely pelletized with one-step-granulating method, is added after dry
Enter superfine silica gel powder, magnesium stearate, mix, crosses 24 meshes；For tabletting after measurement iron content.
C, the inclusion of folic acid
1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 250g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, mistake
Filter, 50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.
D, the preparation of folic acid immediate-release granules
The folic acid and lactose of release layer beta-cyclodextrin inclusion compound are weighed in prescription ratio, sieving is uniformly mixed.With 2% poly- dimension
Ketone K30Softwood is made as adhesive in ethanol solution, crosses the granulation of 20 meshes, and micro mist silicon is added in the whole grain after 40 DEG C of heated-air dryings
Glue, magnesium stearate mix, spare after measurement granule content.
E, compacting is double according to a conventional method in bi-layer tablet press for the particle that the particle and D step that above-mentioned step B obtains obtain
Synusia to get.
In a further preferred embodiment, the technical solution of complex ferrous sulfate sustained release preparation of the invention is as follows:
Prescription
Preparation method method:
A, the preparation of dried ferrous sulfate
After medicinal ferrous sulfate (CP2000 standard contains 7 crystallizations water) is crushed with Universalpulverizer, 80 meshes are crossed, in
40-45 DEG C heated-air drying 36-48 hours, crushed, sieved with 100 mesh sieve with Universalpulverizer after cooling, it is qualified after measured (to meet
The BP1988 editions standards in relation to dried ferrous sulfate) it is spare afterwards.
B, it is sustained the preparation of ferrous sulfate particle
Dried ferrous sulfate and lactose, microcrystalline cellulose and HPMCk100First mix spare, famille rose 60, PVP K30 use
40% (w/v) ethyl alcohol dissolves, and is added in the above-mentioned mixed powder being pre-mixed, and is routinely pelletized with one-step-granulating method, is added after dry
Enter superfine silica gel powder, magnesium stearate, mix, crosses 24 meshes；For tabletting after measurement iron content.
C, the inclusion of folic acid
1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 250g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, mistake
Filter, 50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.
D, the preparation of folic acid immediate-release granules
The folic acid and lactose of release layer beta-cyclodextrin inclusion compound are weighed in prescription ratio, sieving is uniformly mixed.With 2% poly- dimension
Softwood is made as adhesive in ketone K30 ethanol solution, crosses the granulation of 20 meshes, and micro mist silicon is added in the whole grain after 40 DEG C of heated-air dryings
Glue, magnesium stearate mix, spare after measurement granule content.
E, the particle that the particle and D step that above-mentioned step B obtains obtain suppresses double-layer tablets by well-established law in bi-layer tablet press,
To obtain the final product.
In a most preferred embodiment, the technical solution of complex ferrous sulfate sustained release preparation of the invention is as follows:
Prescription
Preparation method method:
A, the preparation of dried ferrous sulfate
After medicinal ferrous sulfate (CP2000 standard contains 7 crystallizations water) is crushed with Universalpulverizer, 80 meshes are crossed, in
40-45 DEG C heated-air drying 36-48 hours, crushed, sieved with 100 mesh sieve with Universalpulverizer after cooling, it is qualified after measured (to meet
The BP1988 editions standards in relation to dried ferrous sulfate) it is spare afterwards.
B, it is sustained the preparation of ferrous sulfate particle
Dried ferrous sulfate and lactose, microcrystalline cellulose and HPMCk100First mix spare, famille rose 60, PVP K30 use
40% (w/v) ethyl alcohol dissolves, and is added in the above-mentioned mixed powder being pre-mixed, and is routinely pelletized with one-step-granulating method, is added after dry
Enter superfine silica gel powder, magnesium stearate, mix, crosses 24 meshes；For tabletting after measurement iron content.
C, the inclusion of folic acid
1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 250g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, mistake
Filter, 50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.
D, the preparation of folic acid immediate-release granules
The folic acid and lactose of release layer beta-cyclodextrin inclusion compound are weighed in prescription ratio, sieving is uniformly mixed.With 2% poly- dimension
Softwood is made as adhesive in ketone K30 ethanol solution, crosses the granulation of 20 meshes, and micro mist silicon is added in the whole grain after 40 DEG C of heated-air dryings
Glue, magnesium stearate mix, spare after measurement granule content.
E, the particle that the particle and D step that above-mentioned step B obtains obtain suppresses double-layer tablets by well-established law in bi-layer tablet press,
To obtain the final product.
The present invention provides a kind of preparation method of above-mentioned complex ferrous sulfate sustained release preparation, and this method includes the system of slow release layer
Standby and release layer preparation, wherein the preparation of the slow release layer includes preparation and the sustained release ferrous sulfate of dried ferrous sulfate
The preparation of grain；The preparation of the release layer includes the preparation of the inclusion and folic acid immediate-release granules of folic acid；
Wherein, the preparation of the dried ferrous sulfate be included in 40-45 DEG C it is 36-48 hours dry；
Wherein, the inclusion of the folic acid includes that folic acid is dissolved in dehydrated alcohol, and cyclodextrin is added, and is stirred, dry；
Wherein, mixing time be 0.5~10 hour, preferably 1~3 hour, drying temperature be 10~80 DEG C, preferably 30
~50 DEG C.
Complex ferrous sulfate preparation provided by the present invention, the first step are to prepare medicinal anhydrous slufuric acid ferrous iron；Second step is
Prepare slow-releasing granules；Third step is to prepare folic acid inclusion compound；4th step is to prepare immediate-release granules；5th step is to prepare sustained release quick-release
Double-layer tablets.Its release in vitro requirement are as follows: ferrous sulfate is discharged completely between 8~10 hours, and is no less than in 2 hours burst sizes
The 50% of total amount.
Tabletting again after the present invention wraps up folic acid with cyclodextrin, preferably solves the stability problem of folic acid, makes the system
The curative effect and stability of agent are ensured.Its advantage is as follows:
(1) slow release layer is made in ferrous sulfate, enables drug slow release.Common Feosol enters stomach
It is disintegrated in 15 minutes, discharges a large amount of iron ion, stronger stimulation is generated to gastrointestinal mucosa, often to the patient for having gastrointestinal disease
It is not resistant to.Iron ion reduces the stimulation to stomach in enteron aisle slow release after using sustained release agent instead.
(2) folic acid and ferrous sulfate are formed into compound, while overcoming afoliate acid and hypoferric anemia, due also to folic acid
The slightly sour environment for causing enteron aisle, be conducive to ferrous sulfate with ferrous state exist be not the raising with pH value and aoxidize it is heavy
It is solidifying, influence the absorption of iron ion.
(3) tabletting again after wrapping up folic acid with cyclodextrin, preferably solves the stability problem of folic acid, makes said preparation
Curative effect and stability are ensured.
Detailed description of the invention
Fig. 1 is release profiles of the ferrous sulfate in 0.1mol dissolving with hydrochloric acid medium.
Specific embodiment
Now with preparation 1000, for every 46.5mg containing dried ferrous sulfate, folic acid 0.35mg.Exemplary narration is such as
Under:
1 complex ferrous sulfate sustained release preparation of embodiment
Prescription
It is sustained layer weight: quick-release layer weight: 324.48:229.9=1.41:1.
Preparation method method:
A, the preparation of dried ferrous sulfate
After medicinal ferrous sulfate (CP2000 standard contains 7 crystallizations water) is crushed with Universalpulverizer, 80 meshes are crossed, in
40-45 DEG C heated-air drying 36-48 hours, crushed, sieved with 100 mesh sieve with Universalpulverizer after cooling, it is qualified after measured (to meet
The BP1988 editions standards in relation to dried ferrous sulfate) it is spare afterwards.
B, it is sustained the preparation of ferrous sulfate particle
Dried ferrous sulfate and lactose, HPMCk100Microcrystalline cellulose first mixes spare, carmine 60,30 POVIDONE K 30 BP/USP30With
40% (w/v) ethyl alcohol dissolves, and is added in the above-mentioned mixed powder being pre-mixed, and is routinely pelletized with one-step-granulating method, is added after dry
Enter superfine silica gel powder, magnesium stearate, mix, crosses 24 meshes；For tabletting after measurement iron content.
C, the inclusion of folic acid
1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 250g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, mistake
Filter, 50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.
D, the preparation of folic acid immediate-release granules
Release layer cyclodextrin encapsulated folic acid and lactose are weighed in prescription ratio, sieving is uniformly mixed.With 2% povidone
K30Softwood is made as adhesive in ethanol solution, crosses 20 meshes and pelletizes, the whole grain after 40 DEG C of heated-air dryings, addition superfine silica gel powder,
Magnesium stearate mixes, spare after measurement granule content.
E, above-mentioned B particle and D particle suppress double-layer tablets by well-established law in bi-layer tablet press, make ferrous sulfate and leaf in tablet
The content of acid meets the requirements to obtain the final product, inspection after packaging.Made tablet shines drug release determination method, is with 0.1mol hydrochloric acid 1000ml
Medium, 100 revs/min of revolving speed；Determination data see the table below 1.
1 drug release determination data (%) of table
| 0 | 1h | 2h | 4h | 8h | 12h | |
| Embodiment 1 | 0 | 30 | 45 | 60 | 86 | 100 |
The influence of 2~4 different viscosities sustained-release agent of embodiment
Using method same as Example 1, wherein sustained-release agent uses the type of table 2.
Table 2
The made tablet of embodiment 2~4 is shone into drug release determination method, using 0.1mol hydrochloric acid 1000ml as medium, revolving speed 100
Rev/min；Determination data see the table below shown in 3.
3 drug release determination data (%) of table
| Test serial number | 0 | 1h | 2h | 4h | 8h | 12h |
| Embodiment 1 | 0 | 30 | 45 | 60 | 86 | 100 |
| Embodiment 2 | 0 | 11 | 22 | 32 | 41 | 53 |
| Embodiment 3 | 0 | 8 | 13 | 21 | 31 | 35 |
| Embodiment 4 | 0 | 50 | 76 | 101 | 100 |
The influence of 5~7 sustained-release agent dosage of embodiment
Using method same as Example 1, wherein the dosage of the sustained-release agent using table 4
The dosage (gram) of 4 sustained-release agent of table
| Ferrous sulfate | HPMCK100 | HPMCK100 | HPMCK100 | |
| Embodiment 5 | 74.5 | 56 (10%) | ||
| Embodiment 6 | 74.5 | 112 (20%) | ||
| Embodiment 7 | 74.5 | 168 (30%) |
The made tablet of embodiment 5~7 is shone into drug release determination method, using 0.1mol hydrochloric acid 1000ml as medium, revolving speed 100
Rev/min；Determination data see the table below shown in 5:
5 drug release determination data (%) of table
| 0h | 1h | 2h | 4h | 8h | 12h | |
| Embodiment 5 | 0 | 49 | 90 | 100 | 100 | |
| Embodiment 6 | 0 | 23 | 40 | 52 | 62 | 81 |
| Embodiment 7 | 0 | 13 | 21 | 32 | 40 | 53 |
Embodiment 8
After preparing slow-releasing granules and folic acid inclusion particle by 1 method of embodiment, two kinds of particles are uniformly mixed, compacting is normal
Rule, obtain single-layer sheet.
Embodiment 9
In addition to the inclusion of folic acid, other are same as Example 1.The inclusion of folic acid is carried out by 1:100, method and embodiment
1 is identical.1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 100g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, is filtered,
50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.
Embodiment 10
In addition to the inclusion of folic acid, other are same as Example 1.The inclusion of folic acid is carried out by 1:400, method and embodiment
1 is identical.1g folic acid is taken, is dissolved in 400ml dehydrated alcohol, 400g beta-cyclodextrin is added with stirring, is stirred at room temperature 2 hours, is filtered,
50ml ethanol washing, 40 DEG C are dried in vacuo, for tabletting after measurement folate content.Since beta-cyclodextrin dosage is too big, lead to speed
It is too big to release layer grain amount, suitable double-layer tablets can not be pressed into.
11 accelerated test of embodiment
The double-layer tablets of the double-layer tablets of Example 1, the single-layer sheet of embodiment 8 and embodiment 9, it is commercially available: Ferrograd
The tablet (TEOFARMA s.r.l, Italy) of Folic carries out 6 months accelerated tests (40 DEG C of temperature, relative humidity 75%), examines
Examine folic acid stability.Data see the table below 6 and show.
The content (labelled amount %) of folic acid in 6 speed test of table
Data explanation: being included and suppressed using folic acid double-layer tablets, reduce the contact surface of folic acid and slow release layer, can be greatly
Improve the stability of folic acid.
Claims (44)
1. a kind of complex ferrous sulfate sustained release preparation, which includes slow release layer and release layer, wherein the slow release layer packet
Include ferrous sulfate, sustained-release agent and the first excipient；The release layer includes the folic acid and the second excipient wrapped up with cyclodextrin；
Wherein, the sustained-release agent is the hydroxypropyl methyl cellulose of 100mpa.s.
2. sustained release preparation according to claim 1, which is characterized in that in the slow release layer, the first excipient choosing
From one of filler, pigment, adhesive, lubricant and glidant or a variety of.
3. sustained release preparation according to claim 2, which is characterized in that in first excipient, the filler choosing
From one of starch, dextrin, Icing Sugar, lactose and microcrystalline cellulose or a variety of.
4. sustained release preparation according to claim 2, which is characterized in that in first excipient, the filler is
Lactose and microcrystalline cellulose.
5. sustained release preparation according to claim 2, which is characterized in that in first excipient, the pigment is normal
With natural or synthetic edible pigment.
6. sustained release preparation according to claim 2, which is characterized in that in first excipient, the pigment is red
Color edible pigment.
7. sustained release preparation according to claim 2, which is characterized in that in first excipient, the pigment is rouge
Rouge red 60.
8. sustained release preparation according to claim 2, which is characterized in that in first excipient, described adhesive is
Natural or synthetic medicinal adhesive.
9. sustained release preparation according to claim 2, which is characterized in that in first excipient, described adhesive is
PVP。
10. sustained release preparation according to claim 2, which is characterized in that in first excipient, described adhesive is
PVPk30。
11. sustained release preparation according to claim 2, which is characterized in that in first excipient, the lubricant is
Stearic acid or its salt.
12. sustained release preparation according to claim 2, which is characterized in that in first excipient, the lubricant is
Magnesium stearate.
13. sustained release preparation according to claim 2, which is characterized in that in first excipient, the glidant choosing
From one of talcum powder and superfine silica gel powder or a variety of.
14. sustained release preparation according to claim 2, which is characterized in that in first excipient, the glidant is
Superfine silica gel powder.
15. sustained release preparation according to claim 2, which is characterized in that in first excipient, the glidant is
Gas phase superfine silica gel powder.
16. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the slow release layer
Sustained-release agent accounts for the 10%~40% of the sustained release preparation total weight.
17. sustained release preparation according to claim 16, which is characterized in that in the slow release layer, the sustained-release agent accounts for institute
State the 15%~25% of sustained release preparation total weight.
18. sustained release preparation according to claim 16, which is characterized in that in the slow release layer, the sustained-release agent accounts for institute
State the 15-19% of sustained release preparation total weight.
19. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the slow release layer
Ferrous sulfate accounts for the 10% ~ 30% of the sustained release preparation total weight.
20. sustained release preparation according to claim 19, which is characterized in that in the slow release layer, the ferrous sulfate is accounted for
The 5 ~ 15% of the sustained release preparation total weight.
21. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the slow release layer
First excipient accounts for the 5%~50% of the sustained release preparation total weight.
22. sustained release preparation according to claim 21, which is characterized in that in the slow release layer, first excipient
Account for the 15%~25% of the sustained release preparation total weight.
23. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the release layer
Cyclodextrin is selected from alpha-cyclodextrin, one of beta-cyclodextrin and gamma-cyclodextrin or a variety of.
24. sustained release preparation according to claim 23, which is characterized in that in the release layer, the cyclodextrin is β-
Cyclodextrin.
25. sustained release preparation according to claim 23, which is characterized in that in the release layer, the cyclodextrin is hydroxyl
Propyl-beta-cyclodextrin.
26. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the release layer
Second excipient is selected from one of filler, adhesive, lubricant and glidant or a variety of.
27. sustained release preparation according to claim 26, which is characterized in that in the release layer, in second figuration
In agent, the filler is lactose or starch.
28. sustained release preparation according to claim 26, which is characterized in that in second excipient, described adhesive
Selected from natural or synthetic medicinal adhesive.
29. sustained release preparation according to claim 28, which is characterized in that in second excipient, described adhesive
For medicinal PVP.
30. sustained release preparation according to claim 28, which is characterized in that in second excipient, described adhesive
For PVPk30。
31. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that in second excipient,
The lubricant is stearic acid or its salt.
32. sustained release preparation according to claim 31, which is characterized in that in second excipient, the lubricant
For magnesium stearate.
33. sustained release preparation according to claim 26, which is characterized in that in second excipient, the glidant
Selected from one of talcum powder and superfine silica gel powder or a variety of.
34. sustained release preparation according to claim 33, which is characterized in that in second excipient, the glidant
For superfine silica gel powder.
35. sustained release preparation according to claim 33, which is characterized in that in second excipient, the glidant
For gas phase superfine silica gel powder.
36. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the release layer
With in the folic acid of cyclodextrin package, the mass ratio between the folic acid and the cyclodextrin is 1:50~500.
37. sustained release preparation according to claim 36, which is characterized in that described with cyclodextrin packet in the release layer
In the folic acid wrapped up in, the mass ratio between the folic acid and the cyclodextrin is 1:200~400.
38. sustained release preparation according to claim 36, which is characterized in that described with cyclodextrin packet in the release layer
In the folic acid wrapped up in, the mass ratio between the folic acid and the cyclodextrin is 1:250~300.
39. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the release layer
With cyclodextrin package folic acid the preparation method is as follows:
Folic acid is dissolved in dehydrated alcohol, cyclodextrin is added, is stirred, it is dry；
Mixing time is 0.5~10 hour,
Drying temperature is 10~80 DEG C.
40. sustained release preparation according to claim 39, which is characterized in that mixing time is 1~3 hour, and drying temperature is
30~50 DEG C.
41. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that described in the release layer
The 5%~25% of the sustained release preparation total weight is accounted for the folic acid that cyclodextrin wraps up；
In the release layer, second excipient accounts for the 5%~30% of the sustained release preparation total weight.
42. sustained release preparation according to claim 41, which is characterized in that described with cyclodextrin packet in the release layer
The folic acid wrapped up in accounts for the 10%~20% of the sustained release preparation total weight；
In the release layer, second excipient accounts for the 10%~20% of the sustained release preparation total weight.
43. according to claim 1 to sustained release preparation described in any one of 15, which is characterized in that in the slow release layer, institute
Stating the weight ratio between slow release layer and the release layer is 1~2:1.
44. sustained release preparation according to claim 43, which is characterized in that in the slow release layer, the slow release layer and institute
Stating the weight ratio between release layer is 1~1.5:1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201810651665.7A CN108524461B (en) | 2018-06-22 | 2018-06-22 | A kind of complex ferrous sulfate sustained release preparation |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810651665.7A CN108524461B (en) | 2018-06-22 | 2018-06-22 | A kind of complex ferrous sulfate sustained release preparation |
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| CN108524461A CN108524461A (en) | 2018-09-14 |
| CN108524461B true CN108524461B (en) | 2019-08-16 |
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| CN109701027A (en) * | 2019-01-24 | 2019-05-03 | 北京斯利安药业有限公司 | A kind of folic acid pharmaceutical composition and folic acid pharmaceutical preparation of novel enhancing folic acid antioxidant |
| CN116509893A (en) * | 2023-06-07 | 2023-08-01 | 安徽省慧灵生物科技有限公司 | Compound mineral vitamin slow-release preparation |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322778A (en) * | 2008-07-22 | 2008-12-17 | 北京康比特体育科技股份有限公司 | Double-layer sustained release tablets for compensating iron and preparation thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR100422350B1 (en) * | 2001-06-28 | 2004-03-12 | 주식회사 하이닉스반도체 | A method for fabricating capacitor |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101322778A (en) * | 2008-07-22 | 2008-12-17 | 北京康比特体育科技股份有限公司 | Double-layer sustained release tablets for compensating iron and preparation thereof |
Non-Patent Citations (2)
| Title |
|---|
| β-环糊精对叶酸的包合作用研究;杨克迪等;《高校化学工程学报》;20110831;第25卷(第4期);699-702 |
| 复方硫酸亚铁缓释片中两组份的含量测定;王林等;《安徽医药》;20061031;第10卷(第8期);579-580 |
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