CN109549935A - A method of glucocorticoid partial size is reduced by solution mode - Google Patents
A method of glucocorticoid partial size is reduced by solution mode Download PDFInfo
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- CN109549935A CN109549935A CN201710885709.8A CN201710885709A CN109549935A CN 109549935 A CN109549935 A CN 109549935A CN 201710885709 A CN201710885709 A CN 201710885709A CN 109549935 A CN109549935 A CN 109549935A
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- particle
- cortin
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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
- A61K9/1682—Processes
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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
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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
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
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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
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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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
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/007—Pulmonary tract; Aromatherapy
- A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
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- Steroid Compounds (AREA)
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Abstract
The present invention relates to a kind of method for reducing corticosteroid drug partial size by solution mode, the particle obtained using this kind of method can be used in pharmaceutical preparation, so that pharmaceutical preparation has better effect.
Description
Technical field:
The present invention relates to a kind of methods for reducing corticosteroid drug partial size by solution mode, are obtained using this kind of method
Particle can be used in pharmaceutical preparation so that pharmaceutical preparation have better effect.
Background technique
It is well known that glucocorticoid has good effect in treatment inflammation.Glucocorticoid is both normal human
Interior important physiologically substance, and be the immunosuppressor of wide clinical application.In vivo, it is secreted by adrenal cortex glomerular zone
Steroid hormone mainly includes cortisol and cortisone.The clinical glucocorticoid used as drug mainly includes hydrogenation can
Pine, prednisone (prednisone), dexamethasone etc., wherein influence of the dexamethasone to normal endogenous cortisol secretion is the most aobvious
It writes.The pharmacological action of glucocorticoid mainly includes anti-inflammatory, immunosupress, Hemorrhagic shock and antitoxic action.Although glucocorticoid
It is had longer history as anti-inflammatory drug and immunosuppressor in clinical application, curative effect gains public acceptance already, in idicatio, agent
Amount, side effect etc. have accumulated considerable clinical data.Using glucocorticoid as the local injection group of active constituent
Object is closed, can treat muscle skeleton and soft tissue disease: rheumatoid arthritis, such as osteoarthritis, bursal synovitis, tatanic ridge
Vertebra is scorching, epicondylitis, radiculitis, coccyalgia, sciatica, pain in the loins, torticollis, ganglion, epostoma, fascitis etc.
Disease.
The third section 1-4 row of page 261 discloses that " drug in general powder unless otherwise specified should all in evidence 2
Pass through No. six sieves after crushing.Slightly solubility and the slow drug such as salol, camphor, sulfanilamide (SN) etc. of dissolution rate should crush carefully a bit to increase
Add dissolution rate, to improve curative effect；Most fine powder must be made in secondary magnesium carbonate, aluminium hydroxide etc., give full play to its treatment with benefit
Effect；", " solubility of insoluble drug is described in influence of (two) powder physicochemical property to preparation validity of page 237
And dissolution rate absorption of drugs has an impact.The dissolution of insoluble drug is related with its specific surface area, the small then specific surface of particle
Product is big, and solubility property is good, therefore can improve its curative effect.", the evidence page 437 " 3. granularity " partially discloses that " indissoluble or dissolution are slow
Slow drug, partial size are to influence an important factor for absorbing.Partial size is thinner, and surface area is bigger, and solution rate is faster." thus may be used
See, the evidence 2 enlightened for the drug of slightly solubility can by reduce particle so that be reduced to 10 μm hereinafter, molten to increase
Xie Du, to improve the absorption of drug.
It is known that the medicine material medicine usual manner for obtaining lower partial size is to crush.Crushing process be solid material outside
Under power effect, the process that overcomes cohesive force that particle is made to become smaller.There are many kinds of this external force, such as electric power, mechanical force, explosion.Just
For mechanical force, basic grinding mode, which has, squeezes crushing, impact comminution, fricting shearing crushing and splitting crushing etc..
But due to using external force in crushing, it will cause particle heating, under the action of internal residual moisture, can generate miscellaneous
The problems such as matter increases, while will also result in a series of environmental issues such as the excessive, dust of energy consumption.
Summary of the invention
A kind of method in order to preferably obtain new control partial size, scientific research personnel pass through constantly research and test, we
It has surprisingly found that when stirring cortin particle in the phosphinylidyne amine aqueous solution of 1-5%, can grain diameter be reduced
15% or more.
Ethanol water preparation method is by taking 5% carbon amide solution as an example in the present invention: 5g carbamide is to entering 100ml volumetric flask
In, add water to be settled to 100ml.
A method of preparing particle, it is characterised in that cortin particle is stirred in organic aqueous solution, it can be with
So that grain diameter reduces by 15% or more.
The above-mentioned method for preparing cortin particle, it is characterised in that organic aqueous solution is the phosphinylidyne that concentration is 1-5%
Amine aqueous solution.The above-mentioned method for preparing cortin particle, it is characterised in that the phosphinylidyne amine content of the phosphinylidyne amine aqueous solution
For 3-5%.
The above-mentioned method for preparing cortin particle, it is characterised in that the glucocorticoid be dexamethasone, times he
Meter Song, beclomethasone, methylprednisolone, hydrocortisone, prednisone, Mometasone, Triamcinolone acetonide, triamcinolone, budesonide, ring
One or more of Suo Naide, desonide, fluticasone and/or its ester.Glucocorticoid as described in claim 1
Ester, it is characterised in that the ester is the ester that the acid of 1-5 carbon is formed.
The ester of above-mentioned glucocorticoid, it is characterised in that the acid of the 1-5 carbon is acetic acid, propionic acid, butyric acid, isobutyl
One or more of acid, valeric acid, furancarboxylic acid.
The above-mentioned method for preparing cortin particle, it is characterised in that organic aqueous solution is the ethyl alcohol that concentration is 4-10%
Aqueous solution.State the method for preparing cortin particle, it is characterised in that the ethanol content of the ethanol water is 5-8%.
The above-mentioned method for preparing cortin particle, it is characterised in that the glucocorticoid be dexamethasone, times he
Meter Song, beclomethasone, methylprednisolone, hydrocortisone, prednisone, Mometasone, Triamcinolone acetonide, triamcinolone, budesonide, ring
One or more of Suo Naide, desonide, fluticasone and/or its ester
The ester of above-mentioned glucocorticoid, it is characterised in that the ester is the ester that the acid of 1-5 carbon is formed.
The ester of above-mentioned glucocorticoid, it is characterised in that the acid of the 1-5 carbon is acetic acid, propionic acid, butyric acid, isobutyl
One or more of acid, valeric acid, furancarboxylic acid.
The above-mentioned method for preparing cortin particle, it is characterised in that the phosphinylidyne amine content of the phosphinylidyne amine aqueous solution is
3-5%.
The above-mentioned method for preparing cortin particle, it is characterised in that the solubility of the cortin in water is micro-
It is molten, almost insoluble or insoluble.
The application of particle obtained by the above method in medicine preparation.
Particle obtained by the above method is preparing the application in Sucked medicine.
Particle obtained by the above method is preparing the application in oral administration solid drug.
Particle obtained by the above method is preparing the application in external drug.
Application of the particle obtained by the above method in preparation injection drug.
Specific embodiment
One, phosphinylidyne amine aqueous solution reduces partial size mode
Below will by embodiment, the invention will be further described, these description be not the content of present invention is made into
The restriction of one step.It should be understood by those skilled in the art that changing to equivalent replacement made by technical characteristic of the invention, or accordingly
Into still falling within protection scope of the present invention.
Various materials used in the following embodiment are with a batch, and the D90 partial size of cortin raw material is 50 ± 2 μm, such as
For ester or salt, then weight is in terms of proto-drug, such as prednisone acetate, then is with prednisone weight calculation amount.
Embodiment 1-1 to 1-16
Carbamide amount of aqueous solution used is 1000ml
Technique:
In dosing apparatus, after the completion of carbon amide solution is configured according to concentration, cortin is added between 15 to 25 DEG C,
It is filtered after stirring, it is dry.
Embodiment 2-1 to 2-12
Carbamide amount of aqueous solution used is 1000ml
Technique:
In dosing apparatus, after the completion of carbon amide solution is configured according to concentration, cortin is added at 15 to 25 DEG C,
It is filtered after stirring, it is dry.
1 particle size test of test example
The partial size of following embodiment is detected by Malvern particle instrument MS2000MU.
The definition of D90 partial size: the cumulative particle sizes distribution number of a sample reaches partial size corresponding when 90%.Its physics meaning
Justice is that partial size is less than its particle and accounts for 90%.
By experiment it can be proved that stirring hypopallium hormone partial size in phosphinylidyne amine aqueous solution can become smaller, this will be advantageous
In the absorption of drug, while it is also possible that drug crushing is more easier, while cost is advantageously reduced, reduce energy consumption.
Two, ethanol water reduces partial size mode
Various materials used in the following embodiment are with a batch, and the D90 partial size of cortin raw material is 50 ± 2 μm, such as
For ester or salt, then weight is in terms of proto-drug, such as prednisone acetate, then is with prednisone weight calculation amount.
Embodiment 1-1 to 1-16
Ethanol water dosage is 1000ml
Technique:
In dosing apparatus, after the completion of ethanol solution is configured according to concentration, cortin is added at -5 to 0 DEG C, stirs
It is filtered after mixing, it is dry.
Embodiment 2-1 to 2-12
| Example No. | 2-1 | 2-2 | 2-3 | 2-4 | 2-5 | 2-6 |
| Glucocorticoid code | G1 | G1 | G1 | G1 | G1 | G1 |
| Weight (g) | 50 | 50 | 50 | 50 | 50 | 50 |
| Ethanol water concentration | A1 | A2 | A3 | A4 | A5 | A6 |
| Example No. | 2-7 | 2-8 | 2-9 | 2-10 | 2-11 | 2-12 |
| Glucocorticoid code | G2 | G2 | G2 | G2 | G2 | G2 |
| Weight (g) | 50 | 50 | 50 | 50 | 50 | 50 |
| Ethanol water concentration | A1 | A2 | A3 | A4 | A5 | A6 |
Ethanol water dosage is 1000ml
Technique:
In dosing apparatus, after the completion of ethanol solution is configured according to concentration, cortin is added at -5 to 0 DEG C, stirs
It is filtered after mixing, it is dry.
1 particle size test of test example
The partial size of following embodiment is detected by Malvern particle instrument MS2000MU.
The definition of D90 partial size: the cumulative particle sizes distribution number of a sample reaches partial size corresponding when 90%.Its physics meaning
Justice is that partial size is less than its particle and accounts for 90%.
By experiment it can be proved that stirring hypopallium hormone partial size in ethanol water can become smaller, this is beneficial to
The absorption of drug, while it is also possible that drug crushing is more easier, while cost is advantageously reduced, reduces energy consumption.
Claims (10)
1. a kind of method for preparing particle, it is characterised in that stir cortin particle in organic aqueous solution, can make
Obtaining grain diameter reduces by 15% or more.
2. the method for preparing cortin particle as described in claim 1, it is characterised in that organic aqueous solution is that concentration is 1-
5% phosphinylidyne amine aqueous solution.
3. the method for preparing cortin particle as described in claim 1, it is characterised in that the glucocorticoid is ground plug
Meter Song, betamethasone, beclomethasone, methylprednisolone, hydrocortisone, prednisone, Mometasone, Triamcinolone acetonide, triamcinolone, cloth
One or more of desonide, ciclesonide, desonide, fluticasone and/or its ester.
4. the ester of glucocorticoid as described in claim 1, it is characterised in that the ester is the ester that the acid of 1-5 carbon is formed.
5. the ester of glucocorticoid as claimed in claim 4, it is characterised in that the acid of the 1-5 carbon is acetic acid, propionic acid, fourth
One or more of acid, isobutyric acid, valeric acid, furancarboxylic acid.
6. the method for preparing cortin particle as claimed in claim 2, it is characterised in that the carbon of the phosphinylidyne amine aqueous solution
Amide content is 3-5%.
7. the method for preparing cortin particle as described in claim 1, it is characterised in that organic aqueous solution is that concentration is 4-
10% ethanol water.
8. the method for preparing cortin particle as claimed in claim 7, it is characterised in that the ethyl alcohol of the ethanol water
Content is 5-8%.
9. the method for preparing cortin particle as described in claim 1, it is characterised in that the cortin is in water
Solubility is slightly soluble, almost insoluble or insoluble.
10. the application of the particle that method as described in claim 1 obtains in medicine preparation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710885709.8A CN109549935A (en) | 2017-09-27 | 2017-09-27 | A method of glucocorticoid partial size is reduced by solution mode |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710885709.8A CN109549935A (en) | 2017-09-27 | 2017-09-27 | A method of glucocorticoid partial size is reduced by solution mode |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050095206A1 (en) * | 2003-10-30 | 2005-05-05 | Laboratorio Pablo Cassara S.R.L. | Aerosol pharmaceutical solution formulation containing glucocorticoids stable to the storage; method for stabilizing formulations and use of a stabilizer |
| CN103565737A (en) * | 2012-07-25 | 2014-02-12 | 天津金耀集团有限公司 | Compound glucocorticoid eye drops |
| CN104739811A (en) * | 2015-02-27 | 2015-07-01 | 上海臣邦医药科技有限公司 | Glucocorticoid aerosol inhalation suspension and preparation method thereof |
-
2017
- 2017-09-27 CN CN201710885709.8A patent/CN109549935A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050095206A1 (en) * | 2003-10-30 | 2005-05-05 | Laboratorio Pablo Cassara S.R.L. | Aerosol pharmaceutical solution formulation containing glucocorticoids stable to the storage; method for stabilizing formulations and use of a stabilizer |
| CN103565737A (en) * | 2012-07-25 | 2014-02-12 | 天津金耀集团有限公司 | Compound glucocorticoid eye drops |
| CN104739811A (en) * | 2015-02-27 | 2015-07-01 | 上海臣邦医药科技有限公司 | Glucocorticoid aerosol inhalation suspension and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| 徐筱: ""棉织物活性染料微悬浮体轧染染色研发"", 《中国优秀硕士学位论文全文数据库（电子期刊）》 * |
| 郭惠玲等: "《药剂学》", 28 February 2014, 中山大学出版社 * |
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