CN105748503A - Multivitamin pellet containing 5-methyltetrahydrofolate - Google Patents

Multivitamin pellet containing 5-methyltetrahydrofolate Download PDF

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Publication number
CN105748503A
CN105748503A CN201610142682.9A CN201610142682A CN105748503A CN 105748503 A CN105748503 A CN 105748503A CN 201610142682 A CN201610142682 A CN 201610142682A CN 105748503 A CN105748503 A CN 105748503A
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CN
China
Prior art keywords
methyltetrahydrofolate
micropill
coating materials
vitamin
compound vitamin
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Application number
CN201610142682.9A
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Chinese (zh)
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CN105748503B (en
Inventor
黄飞
赵小伟
欧阳康乐
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FERGUSON (WUHAN) BIOTECHNOLOGY Co Ltd
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FERGUSON (WUHAN) BIOTECHNOLOGY Co Ltd
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Priority to CN201610142682.9A priority Critical patent/CN105748503B/en
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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4415—Pyridoxine, i.e. Vitamin B6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7135—Compounds containing heavy metals
    • A61K31/714—Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
    • A61K9/5047—Cellulose ethers containing no ester groups, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5052—Proteins, e.g. albumin
    • A61K9/5057—Gelatin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings

Abstract

The invention belongs to the field of pharmaceutical preparation and discloses a multivitamin pellet containing 5-methyltetrahydrofolate.The multivitamin pellet consists of a pellet core and a coating, and the diameter of the multivitamin pellet is 200-400 micrometers.The multivitamin pellet comprises, by unit dose, 0.3-0.8mg of folic acid, 1-2mg of vitamin B, 1.5-2microgram of vitamin B12, 80-120mg of an excipient and 6-10mg of a coating agent.The multivitamin pellet containing the 5-methyltetrahydrofolate has the advantages that stability of main ingredients under conditions of high temperature, high humidity and high light can be evidently improved, and accordingly medicine validity period is prolonged.

Description

A kind of compound vitamin micropill containing 5-methyltetrahydrofolate
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to a kind of compound dimension containing 5-methyltetrahydrofolate Raw element micropill.
Background technology
5-methyltetrahydrofolate is tissue or the principal mode of blood folic acid, participates in internal multiple important biochemistry Reaction.Vitamin B is filled into while maternity dress 5-methyltetrahydrofolate6And vitamin B12There is prevention Foetus neural tube defect, arteriosclerosis, treatment megaloblastic anemia etc. act on.
5-methyltetrahydrofolate is very poor with the stability of vitamin B6, vitamin B12, high temperature, high humidity, Illumination, oxidation are all easily caused content and decline, and existing 5-methyltetrahydrofolate preparation generally uses and adds Enter protective agent, antioxidant, or labile element is carried out inclusion or microencapsulation process to improve it Stability, but these modes not only complex manufacturing, and effect is undesirable.
Summary of the invention
It is an object of the invention to for defect present in prior art, it is provided that a kind of containing 5-methyl tetrahydrochysene The compound vitamin micropill of folic acid, to improve 5-methyltetrahydrofolate, vitamin B6, vitamin B12's Stable content.
The technical scheme is that
A kind of compound vitamin micropill containing 5-methyltetrahydrofolate, described micropill is by capsule core and coatings Composition, its particle diameter is 200-400 μm, containing following unit dose composition in described micropill:
Preferably, described excipient be microcrystalline Cellulose, sucrose, starch, lactose, silicon dioxide, One or more in Pulvis Talci.
Preferably, possibly together with 1～1.5mg binding agent in described micropill.
It is further preferred that described binding agent is hydroxypropyl methyl cellulose or PVP K30.
Preferably, described coating materials is made up of internal layer coating agent, middle level coating materials and outer layer coating materials, Described internal layer coating agent is one or more in hydroxypropyl methyl cellulose, gelatin, methylcellulose； Described middle level coating materials is acrylic resin；Described outer layer coating materials is ethyl cellulose, paraffin, jade One or more in rice protein.
It is further preferred that described internal layer coating agent, middle level coating materials, the mass ratio of outer layer coating materials It is followed successively by (2～3): (4～6): (0.8～1.5).
The invention has the beneficial effects as follows:
1) present invention can significantly improve principal agent composition stability under high temperature, high humidity and intense light conditions, Thus extend the effect duration of medicine；
2) dissolution rate of principal agent composition is fast, and bioavailability is high；
3) production technology is simple, easy to operate, and repeatability is high, is suitable for big production.
Detailed description of the invention
Below in conjunction with embodiment, the present invention is described in detail, but should not be understood as the present invention The restriction that protection domain is carried out.
Embodiment 1
A kind of compound vitamin micropill containing 5-methyltetrahydrofolate, is made up of following raw material:
Preparation method is as follows:
1) pill: 5-methyltetrahydrofolate, vitamin B6, vitamin B12 are dissolved in 200ml 80% together Ethanol solution obtains containing drug solns；Common process is used to make celphere microcrystalline Cellulose, so After will contain drug solns in fluid bed and be sprayed on celphere and add medicine to, control baking temperature during medicine-feeding It it is 35～40 DEG C.
During pill, the quality of capsule core is had by the consumption of ethanol, concentration and baking temperature to be affected significantly, When concentration of alcohol is low or consumption is big, capsule core moisture is high, easily cause during medicine-feeding 5-methyltetrahydrofolate and The degraded of vitamin；Concentration of alcohol is high or consumption is few, then can increase the hardness of capsule core, thus reduce medicine The dissolution of thing and release, the most also can affect principal agent composition quality uniformity in capsule core.It is dried temperature Degree directly affects the content of principal agent, therefore unsuitable too high.
2) coating: hydroxypropyl methyl cellulose, acrylic resin, ethyl cellulose are dissolved in 80% respectively In ethanol water, obtain mass concentration and be respectively the coating solution of 2%, 4%, 1%, then to fluidisation Spray into above-mentioned three kinds of coating solutions in Chuan, first spray into hydroxypropyl methyl cellulose coating solution, the most again Spray into Eudragit coatings liquid, finally spray into ethylcellulose coat liquid, control during coating to be dried temperature Degree is 35～40 DEG C, and coating i.e. obtains the compound vitamin micropill of the present invention after terminating.
Internal layer hydroxypropyl methyl cellulose acts primarily as buffer action, and acrylic resin is selected in intermediate layer, main If in order to make principal agent composition quickly discharge inside stomach, outer layer ethyl cellulose acts primarily as protection against the tide, keeps away Light etc. act on.The consumption of the concentration of ethanol, the concentration of coating solution and three kinds of coating materials all can affect micro- The quality of ball, concentration of alcohol is low, then moisture is high, thus principal agent can be caused to degrade；Concentration of alcohol Height, then coatings is uneven, and coating effect is poor, does not has the protective effect to principal agent.Coating solution Concentration mainly affects coating effect, and the consumption of three kinds of coating materials is then overall merit coating protected effect, Draw after the most not affecting the absorption release of medicine.
Use above-mentioned technique to prepare micropill about 1000 altogether, size between 200-400 μm, every Containing 5-methyltetrahydrofolate 0.4mg, containing vitamin B6 1.2mg, containing vitamin B12 1.7 μ g.
Embodiment 2
A kind of compound vitamin micropill containing 5-methyltetrahydrofolate, is made up of following raw material:
Preparation method is as follows:
1) pill: be dissolved in by PVP K30 in 70% ethanol water, obtaining mass concentration is 5% PVP K30 solution, then adds poly-dimension by 5-methyltetrahydrofolate, vitamin B6, vitamin B12 In ketone K30 solution, stirring and dissolving；By lactose and cane sugar powder stirring and evenly mixing, add dissolved with principal agent composition PVP K30 solution, stirring, make soft material, then soft material extrusion-spheronization is made micropill, Obtain capsule core after drying；
2) coating: methylcellulose, acrylic resin, zein are dissolved in 80% ethanol respectively water-soluble In liquid, obtain mass concentration and be respectively the coating solution of 3%, 4%, 2%, then spray in fluid bed Above-mentioned three kinds of coating solutions, first spray into methylcellulose coating solution, spray into acrylic resin the most again Coating solution, finally sprays into zein coating solution, and controlling baking temperature during coating is 35～40 DEG C, and coating is tied The compound vitamin micropill of the present invention is i.e. obtained after bundle.
Prepare micropill 1000 altogether, size between 200-400 μm, every methyl tetrahydrochysene leaf Han 5- Acid 0.3mg, containing vitamin B6 2mg, containing vitamin B12 1.5 μ g.
Embodiment 3
A kind of compound vitamin micropill containing 5-methyltetrahydrofolate, is made up of following raw material:
Preparation method is as follows:
1) pill: hydroxypropyl methyl cellulose is dissolved in 80% ethanol water, obtains mass concentration It is the Gonak of 3%, then by 5-methyltetrahydrofolate, vitamin B6, dimension life Element B12 adds in Gonak, stirring and dissolving；Take starch, add and become dissolved with principal agent The Gonak divided, stirring, make soft material, then by soft material extrusion-spheronization Make micropill, obtain capsule core after drying；
2) coating: gelatin, acrylic resin, paraffin are dissolved in 80% ethanol water respectively, It is respectively the coating solution of 1%, 5%, 2% to mass concentration, in fluid bed, then sprays into above-mentioned three kinds Coating solution, first sprays into gelatine glaze liquid, sprays into Eudragit coatings liquid the most again, finally spray Entering paraffin coating solution, controlling baking temperature during coating is 35～40 DEG C, and coating i.e. obtains the present invention after terminating Compound vitamin micropill.
Embodiment 4
A kind of compound vitamin micropill containing 5-methyltetrahydrofolate, is made up of following raw material:
Preparation method is as follows:
1) pill: be dissolved in by PVP K30 in 75% ethanol water, obtaining mass concentration is 3% PVP K30 solution, then adds poly-dimension by 5-methyltetrahydrofolate, vitamin B6, vitamin B12 In ketone K30 solution, stirring and dissolving；Take sucrose, silicon dioxide, stir, add and become dissolved with principal agent The PVP K30 solution divided, stirring, make soft material, then soft material extrusion-spheronization is made micro- Ball, obtains capsule core after drying；
2) coating: hydroxypropyl methyl cellulose is dissolved in together with gelatin in 75% ethanol water, To the internal layer coating liquid that mass concentration is 2%, acrylic resin, paraffin are dissolved in respectively 75% ethanol water In solution, obtain mass concentration be respectively in 4% and 2%, outer layer coating solution, then in fluid bed Spray into above-mentioned three kinds of coating solutions, first spray into internal layer coating liquid, spray into middle level coating solution the most again, Finally spraying into outer layer coating solution, controlling baking temperature during coating is 35～40 DEG C, and coating i.e. obtains after terminating The compound vitamin micropill of the present invention.
Test example stability test
Example 1～4 and common 5-methyltetrahydrofolate multivitamin tablet (main constituent mixes with adjuvant Tabletting after uniformly), place 10 days under conditions of high temperature 60 DEG C, high light 4500LX and high humility 75% After, its content declines Comparative result, see table.
The stability test result of the table 1 Cernevit-12 containing 5 methyl tetrahydrofolates
From stability test it can be seen that 5-methyltetrahydrofolate, vitamin B6, vitamin B12 three kinds Principal agent composition all has content downward trend under high temperature, high light and super-humid conditions, but embodiment 1～4 Stability be significantly better than that common tablet, wherein the stability of embodiment 1 is best.

Claims (6)

1. the compound vitamin micropill containing 5-methyltetrahydrofolate, it is characterised in that: described micro- Ball is made up of capsule core and coatings, and its particle diameter is 200-400 μm, containing following unit in described micropill Dose components:
2. the compound vitamin micropill containing 5-methyltetrahydrofolate as claimed in claim 1, its feature It is: described excipient is microcrystalline Cellulose, sucrose, starch, lactose, silicon dioxide, Pulvis Talci In one or more.
3. the compound vitamin micropill containing 5-methyltetrahydrofolate as claimed in claim 1, its feature It is: possibly together with 1～1.5mg binding agent in described micropill.
4. the compound vitamin micropill containing 5-methyltetrahydrofolate as claimed in claim 3, its feature It is: described binding agent is hydroxypropyl methyl cellulose or PVP K30.
5. the compound vitamin containing 5-methyltetrahydrofolate as described in Claims 1 to 4 any one is micro- Ball, it is characterised in that: described coating materials is by internal layer coating agent, middle level coating materials and outer layer coating materials group Become, described internal layer coating agent be the one in hydroxypropyl methyl cellulose, gelatin, methylcellulose or Multiple；Described middle level coating materials is acrylic resin；Described outer layer coating materials is ethyl cellulose, stone One or more in wax, zein.
6. the compound vitamin micropill containing 5-methyltetrahydrofolate as claimed in claim 5, its feature It is: described internal layer coating agent, middle level coating materials, the mass ratio of outer layer coating materials are followed successively by (2～3): (4～6): (0.8～1.5).
CN201610142682.9A 2016-03-14 2016-03-14 A kind of multi-vitamins pellet containing 5-methyltetrahydrofolate Active CN105748503B (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110237046A (en) * 2019-03-29 2019-09-17 福格森（武汉）生物科技股份有限公司 A kind of preparation method of L-5- methyl tetrahydrofolate micro-capsule

Citations (6)

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US5932624A (en) * 1995-10-17 1999-08-03 Herbert; Victor D. Vitamin supplement composition
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WO2006099233A2 (en) * 2005-03-10 2006-09-21 Sciele Pharma, Inc. Compositions and methods for the treatment of osteoporosis and inflammatory joint disease
US20090054371A1 (en) * 2005-03-01 2009-02-26 Phontiers S.A.R.L Folic acid-, vitamin b6- and vitamin b12-containing agents and the use thereof
CN103118743A (en) * 2010-07-01 2013-05-22 Isis创新有限公司 Treatment of cognitive disorders
CN105030779A (en) * 2015-07-21 2015-11-11 福格森（武汉）生物科技股份有限公司 (6S)-5-methyl tetrahydrophthalic calcium foliate oral nutrition supplement and method for preparing same

Patent Citations (6)

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Publication number Priority date Publication date Assignee Title
US5932624A (en) * 1995-10-17 1999-08-03 Herbert; Victor D. Vitamin supplement composition
CN1471913A (en) * 2003-07-02 2004-02-04 南京天泽医药科技开发有限公司 Micro-pillet preparation of ranitidine
US20090054371A1 (en) * 2005-03-01 2009-02-26 Phontiers S.A.R.L Folic acid-, vitamin b6- and vitamin b12-containing agents and the use thereof
WO2006099233A2 (en) * 2005-03-10 2006-09-21 Sciele Pharma, Inc. Compositions and methods for the treatment of osteoporosis and inflammatory joint disease
CN103118743A (en) * 2010-07-01 2013-05-22 Isis创新有限公司 Treatment of cognitive disorders
CN105030779A (en) * 2015-07-21 2015-11-11 福格森（武汉）生物科技股份有限公司 (6S)-5-methyl tetrahydrophthalic calcium foliate oral nutrition supplement and method for preparing same

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Title
谢薇等: "复方维生素B6缓释微丸胶囊的制备及质量控制", 《药学进展》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN110237046A (en) * 2019-03-29 2019-09-17 福格森（武汉）生物科技股份有限公司 A kind of preparation method of L-5- methyl tetrahydrofolate micro-capsule
CN110237046B (en) * 2019-03-29 2021-07-30 福格森（武汉）生物科技股份有限公司 Preparation method of L-5-methyltetrahydrofolic acid microcapsules

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