CN109010316A - A kind of preparation method of vitamin B 6 sustained release preparation - Google Patents
A kind of preparation method of vitamin B 6 sustained release preparation Download PDFInfo
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- CN109010316A CN109010316A CN201711109714.6A CN201711109714A CN109010316A CN 109010316 A CN109010316 A CN 109010316A CN 201711109714 A CN201711109714 A CN 201711109714A CN 109010316 A CN109010316 A CN 109010316A
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- solution
- vitamin
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- sustained release
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- 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
- 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
- A61K9/5015—Organic compounds, e.g. fats, sugars
-
- 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
- A61K9/5031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)
-
- 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
-
- 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
- A61K9/5089—Processes
Abstract
The present invention provides a kind of preparation method of vitamin B 6 sustained release preparation, the steps include: to be dissolved in vitamin B6 in 95% ethyl alcohol, obtains solution A, hydroxypropylβ-cyclodextrin is added in solution A and mannitol obtains solution B；Polylactic acid and polyethylene glycol 200 are dissolved in acetone and obtain solution C, solution B and solution C are mixed into obtain solution D, solution D is transferred in magnetic stirring apparatus, continuous stirring solution D12 hours, solution D temperature is down to 0 DEG C~1 DEG C in 2 hours again and stands 12 hours, maintains solution D temperature at 0 DEG C~1 DEG C during standing.Solution D is heated after standing 12 hours, is continuously stirred when solution D temperature rises to 15 DEG C~18 DEG C, solution D temperature is controlled at 15 DEG C~18 DEG C when stirring, obtains vitamin B 6 sustained release preparation with low temperature spray drying legal system after continuously stirring 12 hours.Capsule material dosage of the present invention is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, and drug release is stablized, and has the characteristics that sustained release.
Description
Technical field:
The present invention relates to a kind of pharmaceutical preparation of medicine-carrying polymer preparation more particularly to a kind of vitamin B 6 sustained release preparations
Preparation method.
Background technique:
Hydroxypropylβ-cyclodextrin is a kind of ideal injection solubilizer and drug excipient in medical industry.It can be with
The water solubility of insoluble drug is improved, increases medicine stability, improve drug bioavailability, the curative effect of medicament is made to increase or take
Dosage is reduced, and adjustable or control drug rate of release reduces poisonous side effect of medicine.Can be used for oral drugs, injection,
Mucoadhesive delivery system (including schneiderian membrane, rectum, cornea etc.), Transdermal absorption drug delivery system, lipophilicity targeted drug carrier.
Polylactic acid has tight security to human body, has good biocompatibility and biodegradability, is widely used
In medicament slow release.Currently, the preparation method of polylactic acid drug bearing microsphere mainly has phase separation method, emulsion-solvent evaporation method, spray-on process
Deng.
Vitamin B6 is also known as pyridoxine comprising pyridoxol, pyridoxal and pyridoxamine are deposited in the form of phosphate in vivo
It is being a kind of water soluble vitamin, the constituent of the internal certain coenzyme of vitamin B6 behaviour participates in a variety of metabolic responses, especially
It is that have substantial connection with amino acid metabolism.Clinically using vitamin B6 prevention and treatment artery sclerosis, cholesterol excessively high, cystitis,
Phrenoblabia, neurological disorder, vomiting, the hand postoperative vomiting at the initial stage that is pregnant etc., vitamin B6 can also slow down insulin therapy glycosuria
The vascular complication of disease.Constant slow release at a predetermined rate after the administration of vitamin B6 oral slow-releasing preparation, rather than tradition
Preparation can rapid delivery of pharmaceuticals.With corresponding ordinary preparation, such as fast-release tablet, capsule, oral solution is compared, and the suitable of patient can be improved
Answering property simultaneously increases curative effect of medication.The major advantage of sustained release preparation is can to reduce dosage frequency and avoid taking ordinary preparation
Existing blood concentration peak valley phenomenon.Sustained release preparation can keep blood concentration to stablize in effective blood medicine within the relatively long time
In concentration range, to improve Drug safety.Vitamin B 6 sustained release preparation mainly uses skeleton agent technology to produce at present, often
With ethyl cellulose, acrylic resin, lactose, the auxiliary materials such as microcrystalline cellulose.But there is burst release with the dosage form that such technology produces
The risk changed with drug release during storage, and supplementary product consumption is big, is unfavorable for taking orally.There is provided a kind of safety to this for clinic has
Effect, reliable in quality, high production efficiency, supplementary product consumption is moderate, and the stable vitamin B 6 sustained release preparation of drug release is necessary, mirror
In this, the present invention is proposed.
Summary of the invention:
The technical problem to be solved by the present invention lies in overcoming the defects of the prior art, provides a kind of safe and effective, quality
Reliably, high production efficiency, supplementary product consumption is moderate, the stable vitamin B 6 sustained release preparation and preparation method thereof of drug release.
The technical problems to be solved by the invention are realized using following technical scheme.
A kind of vitamin B 6 sustained release preparation, which is characterized in that the sustained release preparation by vitamin B6, hydroxypropylβ-cyclodextrin,
Polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol and acetone composition.The vitamin B 6 sustained release preparation each component is by weight
Amount containing 95% ethyl alcohol 110~130, contains hydroxypropylβ-cyclodextrin 110~130, contains mannitol 20~30 than containing vitamin B6 100,
Containing acetone 130~150, contain polylactic acid 130~150, contain polyethylene glycol 200 20~40, the polylactic acid relative molecular weight is
5000~20000.
It is a further object to provide a kind of methods for being prepared into vitamin B 6 sustained release preparation, which is characterized in that
The specific steps of this method are as follows:
1) vitamin B6 is dissolved in 95% ethyl alcohol, obtains vitamin B6 solution, is denoted as solution A；
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B；
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into vitamin B 6 sustained release preparation with low temperature spray drying legal system.
Vitamin B 6 sustained release preparation of the invention is passed through to be released with the cumulative in vitro of commercially available same dosage form vitamin B 6 sustained release preparation
Dose comparative study, it was demonstrated that vitamin B 6 sustained release preparation medicine release of the invention is more stable, and slow-release function is more preferable.And it is prepared
Method high production efficiency, capsule material dosage is moderate, and dry materials temperature is low, and obtained carrying medicine is uniform in size, and encapsulation rate is greater than
80%, drugloading rate is greater than 50%.
Detailed description of the invention
Curve a is the extracorporeal accumulating released medicine curve of 1 gained preparation of the embodiment of the present invention in Fig. 1, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form vitamin B 6 sustained release preparation.In Fig. 1, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 2 gained preparation of the embodiment of the present invention in Fig. 2, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form vitamin B 6 sustained release preparation.In Fig. 2, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Curve a is the extracorporeal accumulating released medicine curve of 3 gained preparation of the embodiment of the present invention in Fig. 3, and curve b is commercially available identical
The extracorporeal accumulating released medicine curve of dosage form vitamin B 6 sustained release preparation.In Fig. 3, abscissa is time (hour), and ordinate is
Cumulative release amount (%).
Specific embodiment:
In order to be easy to understand the technical means, the creative features, the aims and the efficiencies achieved by the present invention, tie below
Specific embodiment is closed, the present invention is further explained.
For the consistency of guarantee test result, the embodiment of the present invention has used the raw material of same batch, auxiliary material, and uses
Consistent production technology prepares vitamin B 6 sustained release preparation.
Embodiment one:
1) 100g vitamin B6 is dissolved in 110g95% ethyl alcohol, obtains vitamin B6 ethanol solution, is denoted as solution A；
2) 110g hydroxypropylβ-cyclodextrin and 20g mannitol are added in solution A, obtains solution B；
3) 130g polylactic acid and 20g polyethylene glycol 200 are dissolved in 130g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into vitamin B 6 sustained release preparation, the temperature of spray drying with low temperature spray drying legal system
Degree control is at 55 DEG C, nozzle diameter: 0.5mm, vacuum degree: 0.03MPA, flow: 500ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.61% that gained sample, which measures encapsulation rate, carrying drug ratio 50.35%, body
Outer release experiment proves that this preparation energy slow release vitamin B6, vitamin B6 are finally discharged up to 90% or more, sees Fig. 1.
Embodiment two:
1) 100g vitamin B6 is dissolved in 120g95% ethyl alcohol, obtains vitamin B6 ethanol solution, is denoted as solution A；
2) 120g hydroxypropylβ-cyclodextrin and 25g mannitol are added in solution A, obtains solution B；
3) 140g polylactic acid and 30g polyethylene glycol 200 are dissolved in 140g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into vitamin B 6 sustained release preparation, the temperature of spray drying with low temperature spray drying legal system
Degree control is at 55 DEG C, nozzle diameter: 0.75mm, vacuum degree: 0.035MPA, flow: 700ml/ hours.
Sample obtained by low temperature spray drying is taken, it is 80.02% that gained sample, which measures encapsulation rate, carrying drug ratio 50.78%, body
Outer release experiment proves that this preparation energy slow release vitamin B6, vitamin B6 are finally discharged up to 90% or more, sees Fig. 2.
Embodiment three:
1) 100g vitamin B6 is dissolved in 130g95% ethyl alcohol, obtains vitamin B6 ethanol solution, is denoted as solution A；
2) 130g hydroxypropylβ-cyclodextrin and 30g mannitol are added in solution A, obtains solution B；
3) 150g polylactic acid and 40g polyethylene glycol 200 are dissolved in 150g acetone, obtain polylactic acid and polyethylene glycol 200 is molten
Liquid is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution
D12 hours, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, solution D temperature is maintained during standing
At 0 DEG C~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours,
The control of solution D temperature is at 15 DEG C~18 DEG C when stirring；
7) solution D that step 6 obtains is obtained into vitamin B 6 sustained release preparation with low temperature spray drying legal system,
The temperature of spray drying is controlled at 60 DEG C, and nozzle diameter: 1mm, vacuum degree: 0.04MPA, flow: 1000ml/ is small
When.
Sample obtained by low temperature spray drying is taken, it is 81.02% that gained sample, which measures encapsulation rate, carrying drug ratio 51.28%, body
Outer release experiment proves that this preparation energy slow release vitamin B6, vitamin B6 are finally discharged up to 90% or more, sees Fig. 3.
The basic principles, main features and advantages of the present invention have been shown and described above.The technology of the industry
For personnel it should be appreciated that the present invention is not limited to the above embodiments, described in the above embodiment and specification is only the present invention
Preference, be not intended to limit the invention, without departing from the spirit and scope of the present invention, the present invention also has various
Changes and improvements, these changes and improvements all fall within the protetion scope of the claimed invention.The claimed scope of the invention is by institute
Attached claims and its equivalent thereof.
Claims (5)
1. a kind of preparation method of vitamin B 6 sustained release preparation, it is characterised in that the vitamin B 6 sustained release preparation is by vitamin
B6, hydroxypropylβ-cyclodextrin, polylactic acid, mannitol, polyethylene glycol 200,95% ethyl alcohol, acetone composition.
2. the preparation method of vitamin B 6 sustained release preparation as described in claim 1, it is characterised in that the steps include:
1) vitamin B6 is dissolved in 95% ethyl alcohol, obtains vitamin B6 solution, is denoted as solution A；
2) hydroxypropylβ-cyclodextrin and mannitol are added in solution A, obtains solution B；
3) polylactic acid and polyethylene glycol are dissolved in acetone, obtain polylactic acid and polyethylene glycol 200 solution, is denoted as solution C；
4) solution B and solution C are mixed, obtains solution D；
5) solution D is transferred in magnetic stirring apparatus, controls the temperature of solution D at 15 DEG C~18 DEG C, continuous stirring solution D12 is small
When, then solution D temperature is down to 0 DEG C~1 DEG C in 2 hours and stands 12 hours, maintain solution D temperature at 0 DEG C during standing
~1 DEG C；
6) solution D for obtaining step 5 heats, and continuously stirs when solution D temperature rises to 15 DEG C~18 DEG C 12 hours, stirs
When solution D temperature control at 15 DEG C~18 DEG C；
7) solution D that step 6 obtains is obtained into vitamin B 6 sustained release preparation with low temperature spray drying legal system.
3. vitamin B 6 sustained release preparation each component as claimed in claim 1 or 2 contains vitamin B6 100 by weight, contain 95%
Ethyl alcohol 110~130 contains hydroxypropylβ-cyclodextrin 110~130, contains mannitol 20~30, contains acetone 130~150, contains polylactic acid
130~150, contain polyethylene glycol 200 20~40.
4. the preparation method of vitamin B 6 sustained release preparation as claimed in claim 1 or 2, it is characterised in that opposite point of polylactic acid
Son amount is 5000~20000.
5. the preparation method of vitamin B 6 sustained release preparation as claimed in claim 3, it is characterised in that the temperature of low temperature spray drying
Degree is 55 DEG C~60 DEG C, and nozzle diameter is 0.5mm~1mm, and hothouse vacuum degree is 0.03MPA~0.04MPA, solution D flow
It is 500ml/ hours~1000ml/ hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109714.6A CN109010316A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of vitamin B 6 sustained release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201711109714.6A CN109010316A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of vitamin B 6 sustained release preparation |
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| Publication Number | Publication Date |
|---|---|
| CN109010316A true CN109010316A (en) | 2018-12-18 |
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ID=64628562
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201711109714.6A Withdrawn CN109010316A (en) | 2017-11-11 | 2017-11-11 | A kind of preparation method of vitamin B 6 sustained release preparation |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110252219A (en) * | 2019-07-12 | 2019-09-20 | 宁波工程学院 | A kind of polylactic acid cladding liposoluble vitamin composite material and preparation method |
-
2017
- 2017-11-11 CN CN201711109714.6A patent/CN109010316A/en not_active Withdrawn
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110252219A (en) * | 2019-07-12 | 2019-09-20 | 宁波工程学院 | A kind of polylactic acid cladding liposoluble vitamin composite material and preparation method |
| CN110252219B (en) * | 2019-07-12 | 2021-08-17 | 宁波工程学院 | Polylactic acid coated fat-soluble vitamin composite material and preparation method thereof |
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Application publication date: 20181218 |
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