CN107028893A - The preparation method of Finasteride sustained-release micro-spheres - Google Patents
The preparation method of Finasteride sustained-release micro-spheres Download PDFInfo
- Publication number
- CN107028893A CN107028893A CN201610075637.6A CN201610075637A CN107028893A CN 107028893 A CN107028893 A CN 107028893A CN 201610075637 A CN201610075637 A CN 201610075637A CN 107028893 A CN107028893 A CN 107028893A
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- finasteride
- aqueous phase
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- release micro
- sustained
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- 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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
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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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0034—Urogenital system, e.g. vagina, uterus, cervix, penis, scrotum, urethra, bladder; Personal lubricants
Abstract
The present invention provides a kind of preparation method for treating benign prostatic hyperplasis sustained-release micro-spheres, comprises the following steps：Bulk drug Finasteride is dissolved in sterilized water for injection standby as interior aqueous phase；PLGA (poly (lactic co glycolic acid), PLGA) is dissolved in standby as oil phase in dichloromethane；Prepare concentration standby as outer aqueous phase for 1.0% polyvinyl alcohol water solution；Interior aqueous phase is instilled in oil phase dropwise, colostrum is formed in 20 minutes using ultrasonic emulsification afterwards；After colostrum is stable, colostrum is instilled in outer aqueous phase, magnetic agitation is carried out and handles 4.0 hours；By the said goods kept dry at normal temperatures；Collect microballoon.The formulation of the Finasteride of the present invention, can be used in using interventional therapy operation mode, and the Finasteride sustained-release micro-spheres prepared are delivered into prostate part, curative effect can be greatly improved, toxic side effect is reduced.
Description
Technical field
The present invention relates to drug field, more particularly to a kind of preparation method of Finasteride sustained-release micro-spheres.
Background technology
Finasteride（Finasteride）, it is a kind of 4- aza steroids, it is specific inhibitor of the testosterone metabolism as the desmoenzyme-II type 5a- reductases during stronger dihydrotestosterone.And benign prostatic hyperplasis depend on prostate in conversion from testosterone to dihydrotestosterone.Finasteride belongs to 5 alpha reductase inhibitors, can efficiently reduce blood and intraprostatic dihydrotestosterone, reduces prostate volume and improves symptom, increase uroflow speed, preventing benign prostatic hyperplasia（BPH）Progress.But it is long that oral drugs have the drug effect time, the shortcomings of long-term taking secondary with the whole bodies such as sexual hypoesthesia, impotence, testicular pain, proliferation of mammary gland poison adverse reaction.If Finasteride is prepared into drug bearing microsphere, utilize certain modus operandi, Finasteride drug bearing microsphere is fed directly to prostatic, reach Finasteride microballoon sustained release drugs, prostate local drug concentration can be reached, systemic administration amount can be reduced again, can reduce malicious secondary adverse reaction.
Finasteride preparation has two kinds of formulations of tablet and capsule preparations in the market, therefore it is the problem of those skilled in the art need solution to provide a kind of Finasteride of new formulation.
The content of the invention
In view of the above-mentioned problems, the present invention provides a kind of preparation method for being capable of Finasteride sustained-release micro-spheres of the direct injection to affected part.
To reach above-mentioned purpose, the preparation method of Finasteride sustained-release micro-spheres of the present invention comprises the following steps：
Finasteride is dissolved in sterilized water for injection to aqueous phase in preparing；
PLGA is dissolved in dichloromethane and prepares oil phase；
Prepare concentration and be used as outer aqueous phase for 1.0% polyvinyl alcohol water solution；
Interior aqueous phase is instilled in oil phase dropwise, colostrum is formed in 20 minutes using ultrasonic emulsification afterwards；
After colostrum is stable, colostrum is instilled in outer aqueous phase, magnetic agitation is carried out and handles 4.0 hours；
By the said goods in 8 DEG C of -30 DEG C of preservations；
Dry afterwards；
Collect microballoon.
Further, concentration of the PLGA in oil phase is 0.15g/ml
Further, the Finasteride and the PLGA quality parts ratio are 1:5.
Further, the pH of the oil phase is 6.5.
Further, the volume ratio of the interior aqueous phase, oil phase and outer aqueous phase is 0.6:2:20.
Further, the preparation process is carried out under 8 DEG C of -30 DEG C of temperature conditionss.
Further, the uniform rate of addition that the interior aqueous phase is instilled in the oil phase is 0.5ml/1 ~ 5s.
Further, the uniform rate of addition that the colostrum is instilled in the outer aqueous phase is 0.5ml/1 ~ 5s.
Further, the method for collecting microballoon includes：Using vavuum pump negative-pressure ward, then washed 3 times using distilled water, dried under 8 DEG C of -30 DEG C of temperature conditionss, obtain finished product microballoon.
Beneficial effect
The present invention possesses following beneficial effect with prior art：
The preparation method of the Finasteride sustained-release micro-spheres of the present invention provides a kind of formulation of new Finasteride, Finasteride sustained-release micro-spheres are delivered to by prostatic using certain modus operandi, the Finasteride sustained-release micro-spheres prepared are made locally to be capable of the release of long-time stable in prostate, Finasteride can be made to keep high concentration and long period in lesions position, and it is relatively low in body circulation drug concentration, curative effect can be greatly improved, toxic side effect is reduced.
Brief description of the drawings
Fig. 1 is Finasteride sustained-release micro-spheres ESEM configuration of surface of the present invention（× 110）；
Fig. 2 is Finasteride sustained-release micro-spheres ESEM configuration of surface of the present invention（× 30）；
Fig. 3 is Finasteride experiment in vitro cumulative release amount schematic diagram of the present invention.
Embodiment
The present invention will be further described below in conjunction with the accompanying drawings.
It should be noted that in the case where not conflicting, the feature in embodiment and embodiment in the application can be mutually combined.
The preparation method of Finasteride sustained-release micro-spheres of the present invention, comprises the following steps：
Finasteride is dissolved in sterilized water for injection to aqueous phase in preparing；Sterilized water for injection is medical water, is clinically commonly used,
PLGA is dissolved in dichloromethane and prepares oil phase.
Prepare concentration and be used as outer aqueous phase for 1.0% polyvinyl alcohol water solution；
Interior aqueous phase is instilled in oil phase dropwise, colostrum is formed in 20 minutes using ultrasonic emulsification afterwards；
After colostrum is stable, colostrum is instilled in outer aqueous phase, magnetic agitation is carried out and handles 4.0 hours, obtain Finasteride microballoon；Colostrum is stable to be referred to：Suspension uniformity, no precipitation, granular size is consistent.Without standard.Macroscopic.
Finasteride microballoon is preserved 2 years at 8 DEG C -30 DEG C；
Dry afterwards；
Collect microballoon.
Embodiment 1
The preparation method of the present embodiment Finasteride sustained-release micro-spheres, comprises the following steps：
S100：Finasteride is dissolved in standby as interior aqueous phase in sterilized water for injection；
S200：PLGA is dissolved in standby as oil phase in dichloromethane；Wherein PLGA is（It is poly-（Lactic-co-glycolic acid）Copolymer）；
S300：Prepare concentration standby as outer aqueous phase for 1.0% polyvinyl alcohol water solution；
S400：Interior aqueous phase is instilled in oil phase dropwise, colostrum is formed in 20 minutes using ultrasonic emulsification afterwards；
S500：After colostrum is stable, colostrum is instilled in outer aqueous phase, magnetic agitation is carried out 4.0 hours；
S600：Above-mentioned sample is preserved in normal temperature（8℃-30℃）；
S700：Air drying（8℃-30℃）；
S800：Collect microballoon.
It should be noted that step S100, S200 and S300 can not be carried out by said sequence, i.e. the preparation order of the present invention internal aqueous phase, oil phase and outer aqueous phase is not limited.
The present embodiment is using PLGA as sustained release microsphere agents, and PLGA has good biocompatibility, excellent degradable ability and nontoxic.
Wherein, concentration of the PLGA in oil phase is 0.15g/ml.
Wherein, the quality parts ratio of the Finasteride and the PLGA is 20%.
Wherein, the pH of the oil phase is 6.5.
Wherein, the volume ratio of the interior aqueous phase, oil phase and outer aqueous phase is 0.6:2:20.This ratio is to calculate by volume.
Wherein, the preparation process is at ambient temperature（8℃-30℃）Carry out.
Wherein, the rate of addition that the interior aqueous phase is instilled in the oil phase is 0.5ml/1 ~ 5s.
Wherein, the rate of addition that the colostrum is instilled in the outer aqueous phase is 0.5ml/1 ~ 5s.
Wherein, the method for collecting microballoon is to use vavuum pump negative-pressure ward first, then using distilled water washing 3 times, at ambient temperature finally（8℃-30℃）Dry, obtain finished product microballoon.
Embodiment 2
Raw material：Finasteride pulvis；It is poly-（Lactic-co-glycolic acid）Copolymer（PLGA, 75/25, viscosity：1.0 dl/g）；Polyvinyl alcohol（PVA, purity：96% ~ 98%, degree of hydrolysis：98%, the degree of polymerization：1750±50）；Sterilized water for injection；The reagents such as dichloromethane are that analysis is pure；Equipment includes UV-2550 type ultraviolet specrophotometers；DHG-9070A type electric heating constant-temperature blowing drying boxes；Electric heating constant temperature waters case；Plum Teller electronic balance；A ten thousandth electrooptical balance；The type vacuum freeze driers of Freezone 6；Projection electron microscope；78-1 type magnetic force heating stirrers；SHA-CA type water-bath constant temperature oscillators.
Specifically preparation process is：
S100：Finasteride 80m g are dissolved in 0.3ml sterilizeds water for injection and are used as interior aqueous phase（W1）,
S200：PLGA 0.30g are dissolved in 2ml dichloromethane as oil phase（O）；
S300：The PVA aqueous solution of the 1.0% of 20ml is used as outer aqueous phase（W2）；
S400：By interior aqueous phase（W1）Oil phase is instilled dropwise（O）In, the min of ultrasonic emulsification 20 formation colostrums（W1/O）；
S500：Treat colostrum（W1/O）After stable, by colostrum（W1/O）In the PVA aqueous solution for instilling 1.0% concentration（W2）In, the magnetic agitation 4.0h on 78-1 type magnetic force heating stirrers；
S600：Obtained sample is dried into 24 h at normal temperatures；The equipment used in this step is the type vacuum freeze driers of Freezone 6；
S700：Using vavuum pump negative-pressure ward, then washed 3 times using distilled water, finally dried under conditions of room temperature, obtain finished product microballoon.
The form and particle diameter of the Finasteride sustained-release micro-spheres prepared：Through common om observation, Finasteride-PLGA microsphere features smooth surfaces imporosity is spherical good；Form and particle size are more uniform.Microspherulite diameter is 200 μm of ＜.
The Finasteride sustained-release micro-spheres electron microscopy observation result prepared is shown in Fig. 1, Fig. 2.
The drugloading rate of the Finasteride sustained-release micro-spheres prepared：4.82%.
The envelop rate of the Finasteride sustained-release micro-spheres prepared：81.6%.
The external slow-release time of the Finasteride sustained-release micro-spheres prepared is shown in Fig. 3.As seen in Figure 3, the Finasteride sustained-release micro-spheres that prepared by the present invention slowly discharge in use, can produce slow releasing function for a long time, add up release 65.7% in 840h, with significant slow releasing function.
The external slow-release time of the Finasteride sustained-release micro-spheres prepared is shown in Fig. 3.
The present invention should be understood that; embodiment described above; further details of explanation has been carried out to the purpose of the present invention, technical scheme and beneficial effect; it these are only embodiments of the invention; it is not intended to limit the present invention, every within the spiritual principles of the present invention, made any modification, equivalent substitution and improvements etc.; it should be included in the scope of the protection, the protection domain that protection scope of the present invention should be defined by claim is defined.
Claims (9)
1. a kind of preparation method of Finasteride sustained-release micro-spheres, it is characterised in that comprise the following steps：
Finasteride is dissolved in sterilized water for injection to aqueous phase in preparing；
PLGA is dissolved in dichloromethane and prepares oil phase；
Prepare concentration and be used as outer aqueous phase for 1.0% polyvinyl alcohol water solution；
Interior aqueous phase is instilled in oil phase dropwise, colostrum is formed in 20 minutes using ultrasonic emulsification afterwards；
After colostrum is stable, colostrum is instilled in outer aqueous phase, magnetic agitation is carried out and handles 4.0 hours, obtain Finasteride microballoon；
Finasteride microballoon is preserved 2 years at 8 DEG C -30 DEG C；
Dry afterwards；
Collect microballoon.
2. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that concentration of the PLGA in oil phase is 0.15g/ml.
3. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the Finasteride and the PLGA quality parts ratio are 1: 5.
4. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the pH of the oil phase is 6.5.
5. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the volume ratio of the interior aqueous phase, oil phase and outer aqueous phase is 0.6: 2: 20.
6. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the preparation process is carried out under 8 DEG C of -30 DEG C of temperature conditionss.
7. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the uniform rate of addition that the interior aqueous phase is instilled in the oil phase is 0.5ml/1 to 5s.
8. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the uniform rate of addition that the colostrum is instilled in the outer aqueous phase is 0.5ml/1 to 5s.
9. the preparation method of Finasteride sustained-release micro-spheres according to claim 1, it is characterised in that the method for the collection microballoon includes：Using vavuum pump negative-pressure ward, then washed 3 times using distilled water, dried under 8 DEG C of -30 DEG C of temperature conditionss, obtain finished product microballoon.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109381737A (en) * | 2018-09-29 | 2019-02-26 | 华中科技大学鄂州工业技术研究院 | Load the medicament slow release suppository and its preparation method and application of Finasteride |
| CN110996916A (en) * | 2017-08-18 | 2020-04-10 | 创技公司株式会社 | Microparticles comprising finasteride and methods of making the same |
| WO2020166820A1 (en) * | 2019-02-15 | 2020-08-20 | (주)인벤티지랩 | Composition for subcutaneous injection containing microparticles comprising finasteride |
| CN113081959A (en) * | 2019-12-23 | 2021-07-09 | 创技公司株式会社 | Sustained-release injectable composition containing finasteride |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1965839A (en) * | 2005-11-15 | 2007-05-23 | 上海医药工业研究院 | Sustained release microsphere of finasteride and its analogue, preparation process and use thereof |
| CN101269013A (en) * | 2007-03-23 | 2008-09-24 | 中国科学院过程工程研究所 | Method for preparing polymer microsphere |
| CN102258479A (en) * | 2011-05-04 | 2011-11-30 | 吉林医药学院 | Osteocalcin slow-release microsphere preparation for injection |
| CN103932991A (en) * | 2014-03-28 | 2014-07-23 | 中国人民解放军总医院 | Preparation method of carbazochrome bleeding sustained release microsphere |
| CN103932990A (en) * | 2014-03-28 | 2014-07-23 | 中国人民解放军总医院 | Preparation method of carbazochrome bleeding sustained release microsphere |
-
2016
- 2016-02-03 CN CN201610075637.6A patent/CN107028893A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1965839A (en) * | 2005-11-15 | 2007-05-23 | 上海医药工业研究院 | Sustained release microsphere of finasteride and its analogue, preparation process and use thereof |
| CN101269013A (en) * | 2007-03-23 | 2008-09-24 | 中国科学院过程工程研究所 | Method for preparing polymer microsphere |
| CN102258479A (en) * | 2011-05-04 | 2011-11-30 | 吉林医药学院 | Osteocalcin slow-release microsphere preparation for injection |
| CN103932991A (en) * | 2014-03-28 | 2014-07-23 | 中国人民解放军总医院 | Preparation method of carbazochrome bleeding sustained release microsphere |
| CN103932990A (en) * | 2014-03-28 | 2014-07-23 | 中国人民解放军总医院 | Preparation method of carbazochrome bleeding sustained release microsphere |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110996916A (en) * | 2017-08-18 | 2020-04-10 | 创技公司株式会社 | Microparticles comprising finasteride and methods of making the same |
| CN109381737A (en) * | 2018-09-29 | 2019-02-26 | 华中科技大学鄂州工业技术研究院 | Load the medicament slow release suppository and its preparation method and application of Finasteride |
| WO2020166820A1 (en) * | 2019-02-15 | 2020-08-20 | (주)인벤티지랩 | Composition for subcutaneous injection containing microparticles comprising finasteride |
| CN113081959A (en) * | 2019-12-23 | 2021-07-09 | 创技公司株式会社 | Sustained-release injectable composition containing finasteride |
| US11484495B2 (en) | 2019-12-23 | 2022-11-01 | Inventage Lab Inc. | Sustained-release injectable composition comprising finasteride |
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Application publication date: 20170811 |