CN101642425A - Folic acid enteric preparation composition and preparation method thereof - Google Patents
Folic acid enteric preparation composition and preparation method thereof Download PDFInfo
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- CN101642425A CN101642425A CN200810117696A CN200810117696A CN101642425A CN 101642425 A CN101642425 A CN 101642425A CN 200810117696 A CN200810117696 A CN 200810117696A CN 200810117696 A CN200810117696 A CN 200810117696A CN 101642425 A CN101642425 A CN 101642425A
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- folic acid
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Abstract
The invention discloses a folic acid enteric preparation composition and a preparation method thereof. The composition is mainly prepared from folic acid raw material medicine and proper accessories.The folic acid enteric preparation composition provided by the invention is effective and safe for the improvement of a folic acid preparation, and has the advantages of little stimulation to the stomach so as to reduce the side reaction and the like compared with folic acid stomach tablets. The folic acid enteric preparation composition is particularly applied to pregnant women and patients withstomach upset diseases. The invention provides a new dosage form which is safer and has identical treatment effect; and the preparation process has quality controllability and good stability.
Description
Technical field
The invention belongs to medical technical field, relate to one group of folic acid enteric preparation composition and preparation method thereof.
Background technology
A kind of water solublity vitamin B group that folic acid (Folic acid) is made up of pteridine, para-amino benzoic acid and glutaminic acid residue also is called vitamin(e) M; For body cell growth with breed necessary material.It can help proteinic metabolism; And and vitamin B
12Common erythrocytic generation and the maturation of promoting is to make the indispensable material of erythrocyte.Folic acid works with the form of tetrahydrofolic acid in vivo, and tetrahydrofolic acid participates in the synthetic of purine nucleic acid and pyrimidine nucleotide in vivo and transforms.Folic acid is played the part of important role on manufacturing nucleic acid (ribonucleic acid, DNA (deoxyribonucleic acid)), be the necessary material of human body when utilizing sugar and aminoacid.Human body can not synthesize, and must absorb from the animal plant food.
1, folic acid physiological disposition:
Folic acid enters liver through portal vein after intestinal absorption, in liver under the effect of dihydrofolate reductase, change into and have active tetrahydrofolic acid.The latter is the carrier that shifts " carbon-based group " in the body, is the synthetic principal element of DNA.The oral administration administration almost completely is absorbed at gastrointestinal tract (mainly being duodenal cap), can appear at after 5～20 minutes in the blood, can reach the highest blood drug level after 1 hour.Major part mainly is stored in the liver, and intravital folic acid mainly is broken down into petrin and NSC 71042.Plasma half-life is about 40 minutes.The folic acid that is drained in the intestinal by bile can be absorbed again, forms the liver sausage circulation.
2, folic acid is to the effect of human body:
(1) folic acid can eliminate-poverty blood
Promptly be confirmed as far back as 1948, human (or other animals) can cause megaloblastic anemia and leukopenia as lacking folic acid.Attached Rui Jin hematology of hospital of Shanghai Communications University professor Li Junmin tell the reporter, and the main cause that causes megaloblastic anemia is the synthetic obstacle that occurs of DNA (deoxyribonucleic acid) (being DNA).And vitamin B
12DNA is synthetic necessary just with folic acid, in case body lacks, Anemia will occur.So when treatment, need remove vitimin supplement B12 and folic acid artificially.
(2) folic acid can prevent the neonate deformity,
Research finds that also folic acid is even more important to the anemia of pregnant woman.As lacking folic acid in 3 months at conceived, can cause the fetal neural tube developmental defect, split animal brains, the incidence rate of anencephaly thereby increase.Secondly, the frequent Supplement of folic acid of anemia of pregnant woman can prevent that neonatal weight from kicking the beam, premature labor and baby's cleft palate congenital malformatioies such as (cleftlips).
(3) antitumor action
The foreign study personnel find that folic acid can cause sends out a cancer cell-apoptosis, the gene expression of cancerous cell are had certain influence, so belong to a kind of natural anti-cancer vitamin.
(4) neurocyte and the brain cell development to infant has facilitation
Foreign study shows, adds folic acid in the baby food below 3 years old, helps lend some impetus to its brain cell growth, and the effect that improves intelligence is arranged.FDA (FDA) approved folic acid can make an addition in the baby milk as a kind of health food additive.
(5) folic acid can the prevention of arterial sclerosis
Studies show that folic acid helps the reduction of homocysteine level, and homocysteine can increase apoplexy and cardiopathic risk.In this sense, folic acid should help to keep the unimpeded of tremulous pulse.The intracardiac head of the department Huo Yong of Peking University First Hospital thinks, if but healthy people takes low dose of folic acid for a long time, as 0.4 milligram of every day, is good for the sickness rate that reduces arteriosclerosis, myocardial damage and myocardial infarction etc.(6)
Other effect
Research worker is found both at home and abroad: folic acid can be used as schizophrenia patient's auxiliary therapeutical agent, and it has significant mitigation to this disease.
Generally speaking, folic acid becomes the new a kind of health care vitamin products that emerge on international market after vitamin C, the vitamin E, and its market prospect is very wide.
3, the untoward reaction of folic acid
The folic acid oral formulations of having developed at present has: tablet, capsule, soft capsule etc., but reason owing to dosage form itself, we find in the use: the disintegrate under one's belt of common folic acid gastric solubility preparation, stimulation to stomach is bigger, untoward reaction such as gastrointestinal symptom such as long-term prescription sitophobia can occur, feels sick, abdominal distention are especially to the anemia of pregnant woman (particularly initial stage anemia of pregnant woman) of pregnancy with there is the patient of stomach upset diseases that deficiency in the use is arranged.Be the more reasonable safe instructions for use that existing gastric solubility preparation dosage form can not satisfy doctor and patient fully, more certain use limitation is arranged.
We are through exploring repeatedly, developed one group of folic acid enteric preparation composition, the advantage of this enteric dosage form is: medicine does not dissolve under one's belt, does not cause a series of side effect thereby can not cause to stimulate to stomach, to anemia of pregnant woman and patient's particularly suitable that stomach upset diseases is arranged at conceived initial stage.
Show through relevant patent and prior art literature search result, there is no the relevant report of folic acid enteric preparation composition.
Summary of the invention
In order to overcome the defective that the folic acid gastric soluble tablet exists, we have developed one group of folic acid enteric preparation composition through exploring repeatedly.This enteric coated preparation, medicine does not dissolve under one's belt, does not cause a series of side effect thereby can not cause to stimulate to stomach, and to the anemia of pregnant woman at conceived initial stage with patient's particularly suitable of stomach upset diseases is arranged.
The object of the present invention is to provide one group of folic acid enteric preparation composition and preparation method thereof.
Technical scheme of the present invention is: one group of folic acid enteric preparation composition, said composition are counted 1: 50～5000 compositions by weight by folic acid crude drug and one or more pharmaceutically acceptable pharmaceutical carrier and/or adjuvants.This folic acid enteric preparation specification is 0.2～10mg, and it comprises enteric coated tablet, enteric coated granule and enteric soft or hard capsule.
Described folic acid enteric preparation composition also can further contain carrier and/or adjuvant commonly used in the pharmaceuticals industry, for example binding agent, filler, disintegrating agent, lubricant, wetting agent, fluidizer, antioxidant etc.
Binding agent can be selected the binding agent of mentioning on methylcellulose, polyvinylpyrrolidone and the various preparation book thereof that can play adhesive effect for use.Binding agent can use more than a kind or a kind simultaneously.Binding agent is used to make soft material after can making solution with ethanol or water.
Filler can be selected the water-insoluble filler of mentioning on the various preparation books such as the water-soluble filler mentioned on the various preparation books such as mannitol, trehalose, lactose, sucrose and microcrystalline Cellulose, dextrin, starch, calcium sulfate, calcium phosphate for use.Filler can use more than a kind or a kind simultaneously.
Disintegrating agent can be selected low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, starch and derivant thereof for use, also comprises the disintegrating agent of mentioning on the various preparation books that disintegration is arranged.Disintegrating agent can use more than a kind or a kind simultaneously.
Lubricant can select for use mention on Pulvis Talci, magnesium stearate and the kind preparation book thereof can lubricate lubricant.Lubricant can use more than a kind or a kind simultaneously.
Tablet and granule can be by dry method or wet granulation technology preparations; dry according to a conventional method after the granulation, granulate becomes granule or further tabletting; coating is made enteric coated tablet and enteric coated granule again, and the suitable hybrid particles that enteric soft or hard capsule can be made compositions is filled into to prepare in soft, the hard enteric coated capsule and finishes.
This product is a vitamins, is easy to oxidizedly under air and certain ambient condition, makees film coating so outward appearance can be chosen to be coating solution, increases medicine stability, improves the purpose of tablet appearance.The side effect that film stimulates because this medical instrument has stomach to slit simultaneously so add enteric coating adding on the basis of film-coat, makes medicine disintegrate in small intestinal, to reduce the stomach film stimulation of slitting.
" folic acid enteric preparation composition " of the present invention's development is to change dosage form on existing " YESUAN PIAN " basis, guaranteeing that the former is satisfying under the requirement of dissolution, does not have the variation of matter on the drug effect.This product that changes after the agent is compared with former YESUAN PIAN, and is not only effectively same, quality controllability, good stability, and reduced the side effect to human body of medicine, safety is improved greatly.
The specific embodiment
Embodiment 1 (A1)
Enteric coatel tablets
Prescription:
Folic acid 5.0g
Lactose 25g
Carboxymethyl starch sodium 25g
Starch 45g
The 25%PVP ethanol solution is an amount of
Magnesium stearate 0.5%
??????????????????????????????????????????????????
Make 1000
Preparation technology:
Cross behind 80 mesh sieves folic acid, lactose, carboxymethyl starch sodium, starch standby respectively; taking by weighing starch, lactose, carboxymethyl starch sodium by recipe quantity puts in the mixer behind the mixing and crude drug equivalent incremental method mixing again; it is an amount of to add the 25%PVP ethanol solution; granulation, granulate; 40～45 dryings; dried granule adds 0.5% magnesium stearate mixing; cross 16 eye mesh screen granulate with oscillating granulator; granule is carried out assay; and the heavy scope of definite sheet, tabletting is then with 80% ethanol configuration coating solution; use the coating pan coating, drying.
Embodiment 2 (A2)
Enteric soft capsules
Prescription:
Folic acid 0.2g
Microcrystalline Cellulose 100g
20% alcoholic solution is an amount of
?????????????????????????????????????????????
Make 1000
Preparation technology:
Folic acid, Celluloasun Microcrystallisatum are crossed 80 mesh sieves respectively, take by weighing folic acid by recipe quantity, Celluloasun Microcrystallisatum is put and is mixed 10～15 minutes in the mixer, adds 20% alcoholic solution and makes soft material in right amount, granulates in granulation machine.With the above-mentioned granule that makes in 50 ℃ of dry 30min.Again by oscillating granulator, with 20 eye mesh screen granulate.Hybrid particles is carried out assay, and definite enteric soft capsules shell range of capacity is filled.After the passed examination, packing.
Embodiment 3 (A3)
The enteric hard capsule
Prescription:
Folic acid 1.0g
Dextrin 96g
5% starch slurry is an amount of
????????????????????????????????????????
Make the 1000g grain
Preparation technology:
Folic acid, dextrin are crossed 80 mesh sieves respectively, take by weighing folic acid, dextrin, put and mix 10～15 minutes in the mixer by recipe quantity; add 5% starch slurry and make soft material in right amount, in granulation machine, granulate, with granule in 50 ℃ of dry 30min; again by oscillating granulator, with 20 eye mesh screen granulate.Hybrid particles is carried out assay, and definite enteric hard capsule shell range of capacity is filled.After the passed examination, packing.
Embodiment 4 (A4)
Enteric coated granule
Prescription:
Folic acid 0.4g
Lactose 150g
Microcrystalline Cellulose 200g
The 30%PVP ethanol solution is an amount of
?????????????????????????????????????????????????????
Make 1000g (0.35g/ bag)
Preparation technology:
With folic acid, lactose, microcrystalline Cellulose, cross 100 mesh sieves respectively, take by weighing folic acid, lactose, microcrystalline Cellulose by recipe quantity and in blender, fully mix, add an amount of 30%PVP ethanol solution and make soft material, in granulation machine, granulate.Again with the granule that makes in 50 ℃ of dry 30min, cross 16 eye mesh screen granulate by oscillating granulator, hybrid particles is carried out assay, then with 80% ethanol configuration coating solution coating, drying.
Folic acid enteric preparation composition dissolution confirmatory experiment:
1, method
1.1 instrument and reagent
Instrument: TU-1800SPC ultraviolet-uisible spectrophotometer (Beijing Puxi General Instrument Co., Ltd);
RCZ-6B1 type medicament dissolution instrument (Shanghai Huanghai Sea medicine inspection instrument plant);
BS110S type analysis balance (Beijing Sai Duolisi instrument system company limited).
Reagent: folic acid reference substance (Nat'l Pharmaceutical ﹠ Biological Products Control Institute);
Execute the folic acid enteric preparation that routine 1-embodiment 4 provides;
Other reagent is analytical pure.
1.2 the preparation of reference substance solution
Get that folic acid reference substance 6mg is accurate to be claimed surely, put in the 100mL measuring bottle, add phosphate buffer (pH6.8) and be diluted to scale, get 10mL again and put in the 100mL measuring bottle and be diluted to scale.
1.3 dissolution method
According to dissolution method (two appendix XC of Chinese Pharmacopoeia version in 2000 three therapeutic methods of traditional Chinese medicine) test, be solvent with 0.1mol/l hydrochloric acid 900ml earlier, rotating speed is that per minute 100 changes, operation in accordance with the law in the time of 2 hours, must not have variable color, crack or disintegration phenomenon for test piece; The softgel shell of test sample must not have crack or disintegration phenomenon; Enteric coated particles and release medium all must not have obvious variable color; Discard acid solution in above-mentioned each stripping rotor, add phosphate buffer (pH6.8) 100ml immediately, rotating speed is constant, continues operation in accordance with the law, through 45 minutes, gets subsequent filtrate 25ml and filters, and precision is measured subsequent filtrate 20ml, as need testing solution.
Get two kinds of solution of reference substance and test sample respectively, measure trap at 281nm wavelength place, calculate the stripping quantity of tested folic acid enteric preparation according to spectrophotography.
This product contains the folic acid amount and should be 90.0～110.0% of labelled amount.
2, result:
More than the experimental result of four embodiment list in the following table 1.
Table 1 folic acid enteric preparation composition dissolution determination result
| Sample | Dissolution |
| ??A1 | ??98.4％ |
| ??A2 | ??97.8％ |
| ??A3 | ??97.5％ |
| ??A4 | ??96.7％ |
Conclusion: the folic acid enteric preparation composition dissolution is up to specification.
Claims (9)
1, one group of folic acid enteric preparation composition and preparation method thereof is characterized in that: said composition is counted 1: 50～5000 compositions by weight by folic acid crude drug and one or more pharmaceutically acceptable pharmaceutical carrier and/or adjuvants.
2, described according to claim 1, it is characterized in that this folic acid enteric preparation composition specification is 0.2～10mg, it comprises enteric coated tablet, enteric coated granule and enteric soft or hard capsule.
3, described according to claim 1, it is characterized in that folic acid enteric preparation composition, also can further contain carrier and/or adjuvant commonly used in the pharmaceuticals industry, for example binding agent, filler, disintegrating agent, lubricant, wetting agent, fluidizer, antioxidant etc.
4, pharmaceutical carrier according to claim 3 is characterized in that: wherein binding agent can be selected the binding agent of mentioning on methylcellulose, polyvinylpyrrolidone and the various preparation book thereof that can play adhesive effect for use.Binding agent can use more than a kind or a kind simultaneously.Binding agent is used to make soft material after can making solution with ethanol or water.
5, pharmaceutical carrier according to claim 3 is characterized in that: wherein filler can be selected the water-insoluble filler of mentioning on the various preparation books such as the water-soluble filler mentioned on the various preparation books such as mannitol, trehalose, lactose, sucrose and microcrystalline Cellulose, dextrin, starch, calcium sulfate, calcium phosphate for use.Filler can use more than a kind or a kind simultaneously.
6, pharmaceutical carrier according to claim 3, it is characterized in that: wherein disintegrating agent can be selected low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, microcrystalline Cellulose, cross-linking sodium carboxymethyl cellulose, carboxymethyl starch sodium, starch and derivant thereof for use, also comprises the disintegrating agent of mentioning on the various preparation books that disintegration is arranged.Disintegrating agent can use more than a kind or a kind simultaneously.
7, pharmaceutical carrier according to claim 3 is characterized in that: wherein lubricant can select for use mention on Pulvis Talci, magnesium stearate and the kind preparation book thereof can lubricate lubricant.Lubricant can use more than a kind or a kind simultaneously.
8, described according to claim 1, it is characterized in that described preparation method, coating solution can be made film coating earlier, adds enteric coating adding on the basis of film-coat.
9, described according to claim 1; it is characterized in that in the described preparation method; tablet and granule can be by dry method or wet granulation technology preparations; granulation after drying, granulate become granule or further tabletting; coating is made enteric coated tablet and enteric coated granule again, and enteric soft or hard capsule can be made compositions suitable hybrid particles and be filled into to prepare in soft, the hard enteric coated capsule and finish.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810117696A CN101642425A (en) | 2008-08-04 | 2008-08-04 | Folic acid enteric preparation composition and preparation method thereof |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200810117696A CN101642425A (en) | 2008-08-04 | 2008-08-04 | Folic acid enteric preparation composition and preparation method thereof |
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| CN101642425A true CN101642425A (en) | 2010-02-10 |
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| CN200810117696A Pending CN101642425A (en) | 2008-08-04 | 2008-08-04 | Folic acid enteric preparation composition and preparation method thereof |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102309464A (en) * | 2011-09-21 | 2012-01-11 | 沈阳格林制药有限公司 | Folic acid tablet and preparation method thereof |
| CN103070831A (en) * | 2013-02-02 | 2013-05-01 | 常州市新鸿医药化工技术有限公司 | Method for preparing 10-90% folic acid granules |
| CN104116743A (en) * | 2014-05-21 | 2014-10-29 | 烟台中洲制药有限公司 | Folic acid pharmaceutical composition for preventing administration |
| CN104490802A (en) * | 2014-12-04 | 2015-04-08 | 武汉信嘉和诚药物化学有限公司 | Salidroside enteric-coated tablets and preparation method thereof |
| CN112156096A (en) * | 2020-10-20 | 2021-01-01 | 北京斯利安药业有限公司 | Folic acid sustained-release composition, sustained-release preparation and application thereof |
| CN115040489A (en) * | 2022-08-17 | 2022-09-13 | 北京罗诺强施医药技术研发中心有限公司 | Stable pharmaceutical composition with excellent consistency and process for preparing the same |
-
2008
- 2008-08-04 CN CN200810117696A patent/CN101642425A/en active Pending
Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102309464A (en) * | 2011-09-21 | 2012-01-11 | 沈阳格林制药有限公司 | Folic acid tablet and preparation method thereof |
| CN103070831A (en) * | 2013-02-02 | 2013-05-01 | 常州市新鸿医药化工技术有限公司 | Method for preparing 10-90% folic acid granules |
| CN104116743A (en) * | 2014-05-21 | 2014-10-29 | 烟台中洲制药有限公司 | Folic acid pharmaceutical composition for preventing administration |
| CN104490802A (en) * | 2014-12-04 | 2015-04-08 | 武汉信嘉和诚药物化学有限公司 | Salidroside enteric-coated tablets and preparation method thereof |
| CN104490802B (en) * | 2014-12-04 | 2017-06-20 | 武汉信嘉和诚药物化学有限公司 | Rhodioside enteric coatel tablets and preparation method thereof |
| CN112156096A (en) * | 2020-10-20 | 2021-01-01 | 北京斯利安药业有限公司 | Folic acid sustained-release composition, sustained-release preparation and application thereof |
| CN115040489A (en) * | 2022-08-17 | 2022-09-13 | 北京罗诺强施医药技术研发中心有限公司 | Stable pharmaceutical composition with excellent consistency and process for preparing the same |
| CN115040489B (en) * | 2022-08-17 | 2022-10-25 | 北京罗诺强施医药技术研发中心有限公司 | Stable pharmaceutical composition with excellent consistency and process for preparing the same |
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Open date: 20100210 |