CN102579381A - Guanidine hydrochloride sustained release preparation and preparation method thereof - Google Patents
Guanidine hydrochloride sustained release preparation and preparation method thereof Download PDFInfo
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- CN102579381A CN102579381A CN2012100900241A CN201210090024A CN102579381A CN 102579381 A CN102579381 A CN 102579381A CN 2012100900241 A CN2012100900241 A CN 2012100900241A CN 201210090024 A CN201210090024 A CN 201210090024A CN 102579381 A CN102579381 A CN 102579381A
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Abstract
The invention discloses guanidine hydrochloride sustained release preparation and a preparation method thereof. The guanidine hydrochloride sustained release preparation is mainly prepared by guanidine hydrochloride, a filling agent, sustained release materials and potential of hydrogen (pH) sensitive materials. The preparation method comprises the steps of firstly preparing all raw materials according to proportion, evenly mixing the guanidine hydrochloride, the filling agent, the sustained release materials and the pH sensitive materials at high speed, granulating and drying the evenly mixed powder, finally adding a flow agent, a lubrication agent and an adhesion agent, tableting according to a general method, and achieving guanidine hydrochloride sustained release tablets. The guanidine hydrochloride sustained release preparation is small in side effect, obviously reduces difference of preparation of different batches, improves stability of samples, is convenient long term curing of patients and improves compliance of medicine. A patient can take the guanidine hydrochloride sustained release tablets once a day, so that effective drug concentration in bodies can be guaranteed for 24 hours, and nervous centralis side reactions caused by the fact that a blood concentration peak value is high due to general preparation is reduced.
Description
Technical field
The present invention relates to pharmaceutical field about drug preparation technique, particularly relate to a kind of Guanfacine Hydrochloride slow releasing preparation and preparation method thereof.
Background technology
Guanfacine Hydrochloride belongs to antihypertensive drug, is used to treat moderate to severe hypertension.Chemical name is N-amidino groups-2-(2, the 6-Dichlorobenzene base) acetamide mono-hydrochloric salts, and its molecular formula is: C
9H
9Cl
2N
3OHCl, molecular weight are 282.55, and structural formula is:
Guanfacine Hydrochloride be white to the off-white color crystalline powder, be insoluble in water and ethanol, higher relatively dissolubility (> 30mg/mg is arranged in methanol).
Guanfacine Hydrochloride is selectivity α
2-adrenoceptor synergist is used to treat moderate to severe hypertension the earliest, with the tablet administration of oral administration, at the commodity of U.S. Tenex by name
, specification is 1mg or 2mg.
Because this medicine of Guanfacine Hydrochloride has very strong central action; And this medicine plasma protein binding rate is high; The general formulation rate of release is too fast to make that the blood drug level peak value is higher, brings out its side effect, like drowsiness, dizziness, difficulty falling asleep, feel sick, vomiting, forgetful etc.
SHIRE companies in 2009 have obtained the approval of Guanfacine Hydrochloride slow releasing preparation first at FDA; Because slow release formulation can effectively reduce Cmax; Prolong drug action time; Can be used for the how moving obstacle of new indication-attention deficit (Attention-deficit hyperactivity disorder, treatment ADHD), evident in efficacy; Those children that suffer from ADHD and behavior disorder simultaneously are particularly useful, and the Therapeutic Method of relevant this Guanfacine Hydrochloride slow release medication of United States Patent (USP) protection is arranged.Guanfacine Hydrochloride dissolubility in the solution of different pH is obviously different, has significant pH dependency, and dissolubility is better in acid, and along with the rising of pH, dissolubility significantly reduces.Therefore, usually have following problem between the resulting slow releasing preparation of common method for preparing: pharmacokinetic parameters such as differences between batches are big, release degree poor stability, the interior bioavailability of body are undesirable.
Summary of the invention
The objective of the invention is the defective that exists to Guanfacine Hydrochloride slow releasing preparation traditional preparation process method, providing a kind of is the slow releasing preparation and preparation method thereof of principal agent with the Guanfacine Hydrochloride.Utilize the Guanfacine Hydrochloride slow releasing preparation toxic and side effects of technical scheme preparation of the present invention few, be convenient to patient's long-term treatment, and improved the compliance of medication.Take the Guanfacine Hydrochloride slow releasing tablet of technical scheme preparation of the present invention, take every day and once can guarantee the 24 hours interior active drug concentration of body, and can reduce the higher nervus centralis side reaction that causes of blood drug level peak value that ordinary preparation brings.The present invention has adopted new recipe and new technology to prepare the Guanfacine Hydrochloride slow releasing preparation simultaneously, has significantly reduced the preparation differences between batches and has improved stability of sample.
In order to address the above problem, the technical scheme that the present invention adopts is:
The present invention provides a kind of Guanfacine Hydrochloride slow releasing preparation, representes with weight portion, and said Guanfacine Hydrochloride slow releasing preparation contains 0.2～4 part of Guanfacine Hydrochloride in forming, 10～50 parts of 10～60 parts of filleies and slow-release materials.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said Guanfacine Hydrochloride slow releasing preparation contains 0.4～3 part of Guanfacine Hydrochloride in forming, 25～45 parts of filleies, 10～30 parts of 15～45 parts of slow-release materials and pH sensitive materials.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming, 0.1～1 part of fluidizer, 0.1～10 part of 0.1～1 part of lubricant and binding agent.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 25～45 parts of filleies; 15～45 parts of slow-release materials; 10～30 parts of pH sensitive materials, 0.1～1 part of fluidizer, 0.1～1 part of lubricant and 0.1～10 part of composition of binding agent.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said filler is any one or more in sucrose, lactose, mannitol, starch, microcrystalline Cellulose, Sargassum polysaccharides, citric acid, fumaric acid, tartaric acid, malic acid, succinic acid and the chitosan;
Said slow-release material is any or more than one in ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, Palmic acid and the chitosan;
Said pH sensitive material is any or more than one in polyacrylic acid resin, hydroxyethyl-cellulose acetyl cellulose, cellulose acetate-phthalate ester, cellulose acetate phthalate ester, vinyl acetate phthalate ester, hydroxypropyl methyl cellulose phthalate, Lac and the Hydroxypropyl Methyl Cellulose Phthalate;
Said fluidizer is any one or more in magnesium stearate, Pulvis Talci, hydrogenated vegetable oil and the micropowder silica gel;
Said lubricant is any one or more in Pulvis Talci, hydrogenated vegetable oil, sodium stearyl fumarate, magnesium stearate and the stearyl alcohol;
Said binding agent is any or more than one in water, dehydrated alcohol, water and alcohol mixed solution, Gonak, hydroxypropyl cellulose solution, povidone solution and the carboxymethylcellulose sodium solution.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation, said filler is any or two kinds in lactose and the fumaric acid; Said slow-release material is a hydroxypropyl emthylcellulose, and the methoxyl group substitute proportion is 15%～40% in the hydroxypropyl emthylcellulose, and the hydroxypropyl substitute proportion is 3%～15% (preferred methoxyl group substitute proportion is about 22%, and the hydroxypropyl substitute proportion is about 8%); Said pH sensitive material is the polyacrylic acid resin; Said fluidizer is micropowder silica gel; Said lubricant is any or two kinds in magnesium stearate and the sodium stearyl fumarate; Said binding agent is water or water and alcohol mixed solution.
According to above-mentioned Guanfacine Hydrochloride slow releasing preparation; Said Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 10～40 parts of lactose, 0～20 part of fumaric acid; 10～50 parts of hydroxypropyl emthylcelluloses; 10～40 parts of polyacrylic resins, 0～1 part of micropowder silica gel, 0～1 part of magnesium stearate and 0～10 part of composition of water.
A kind of method for preparing of Guanfacine Hydrochloride slow releasing preparation, said method for preparing may further comprise the steps:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials; At first with mixing in Guanfacine Hydrochloride, filler and slow-release material or Guanfacine Hydrochloride, filler, slow-release material and the pH sensitive material importing high-speed mixer; Obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain the granule of particle diameter less than 14 eye mesh screens; The gained granule is carried out drying; Be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule through the granule of 16 eye mesh screens;
Perhaps prepare various supplementary materials, at first Guanfacine Hydrochloride, filler, slow-release material and pH sensitive material are imported in the high-speed mixer and mix, obtain uniformed powder behind the mix homogeneously according to the supplementary material proportioning of above-mentioned Guanfacine Hydrochloride slow releasing preparation; Add the binding agent for preparing then, adopt the high-speed shearing machine shear granulation, obtain the granule of particle diameter less than 14 eye mesh screens; The gained granule is carried out drying; Be dried to gained granule water content and be no more than 5%, selecting can be through the granule of 16 eye mesh screens, and the fluidizer and the mix lubricant that prepare of adding is even then; According to the conventional method tabletting, process the product Guanfacine Hydrochloride slow releasing tablet of all size at last.
Method for preparing according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is characterized in that: the sheet of said product Guanfacine Hydrochloride slow releasing tablet heavily is 100～350mg; The effective dose of Guanfacine Hydrochloride is that (effective dose that is preferably Guanfacine Hydrochloride in the Guanfacine Hydrochloride slow releasing tablet is 1～4mg) to 0.5～5mg in the products obtained therefrom Guanfacine Hydrochloride slow releasing tablet.
Positive beneficial effect of the present invention:
1, utilizes the Guanfacine Hydrochloride slow releasing preparation toxic and side effects of technical scheme preparation of the present invention few, be convenient to patient's long-term treatment, and improved the compliance of medication.Take the Guanfacine Hydrochloride slow releasing tablet of technical scheme preparation of the present invention, take every day and once can guarantee the 24 hours interior active drug concentration of body, and can reduce the higher nervus centralis side reaction that causes of blood drug level peak value that ordinary preparation brings.The present invention has adopted new recipe and new technology to prepare the Guanfacine Hydrochloride slow releasing preparation simultaneously, has significantly reduced the preparation differences between batches and has improved stability of sample.
2, utilize the Guanfacine Hydrochloride slow releasing preparation of technical scheme preparation of the present invention to have the sustained release performance in the certain hour; What its slow release principle was mainly the present invention's preparation is matrix sustained release tablet; Adjuvant of being selected for use and method for preparing all are easy to get feasible; The suitable suitability for industrialized production that enlarges, the method that is adopted has good repeatability.Particularly the present invention preferably fills a prescription and method for preparing; Be the preferred plan that obtains through screening; Select the prescription of optimization for use, adopt the high speed shear granulation, and pressed disc method prepares slow releasing tablet; The release performance that slow release formulation is good in vivo can be realized, and the different sufferer crowd of slow releasing tablet adaptation of different size can be prepared simultaneously.
Below further specify positive beneficial effect of the present invention through experimental data:
The slow releasing tablet of embodiment 1 preparation is adopted in experiment; Medicine stability investigation method through the pharmacopeia regulation is investigated (referring to 2010 editions two appendix XI X of Pharmacopoeia of People's Republic of China C); Discovery the present invention preferably fills a prescription and has high stability, compares with existing product and prior art to have remarkable result (experimental data sees table 1, table 2 and table 3 for details).
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under table 1 hot conditions
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under table 2 super-humid conditions
The study on the stability of product Guanfacine Hydrochloride slow releasing preparation of the present invention under the table 3 strong illumination condition
In above-mentioned about release degree experiment condition of the present invention:
Leaching condition: the device of dissolution first method, rotating speed are 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer of 900ml, pH 2.2, and detection method is a HPLC.
3, product Guanfacine Hydrochloride slow releasing tablet of the present invention; The preparation process is simple, adopts the high speed shear granulating process, meets the requirement of big production; Under laboratory scale; Can accomplish the amplification production of 10000～30000 units, production efficiency is high, can prepare the Guanfacine Hydrochloride slow releasing tablet of 1～4mg different size.
4, product Guanfacine Hydrochloride slow releasing preparation of the present invention; Show for dynamics research through the body giving drugs into nose; Have the bioavailability equivalence with ordinary preparation, do not produce the problem that reduces bioavailability because of slow releasing function, it discharges model and has reduced blood plasma Chinese medicine peak concentration; Reduce the possibility that has side effects, take the compliance that has improved patient's medication once a day.
5, product Guanfacine Hydrochloride slow releasing preparation of the present invention is investigated through accelerated stability test, in 6 months stable, the medicament contg of character, related substance all in controlled range, suitability for industrialized production.
Four, description of drawings:
The release in vitro degree that Fig. 1 embodiment of the invention 1 gained Guanfacine Hydrochloride slow releasing preparation is three batches.
Five, the specific embodiment:
Further set forth the present invention below in conjunction with embodiment, but do not limit content of the present invention.
Embodiment 1:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, lactose 232.5g, fumaric acid 75g, hydroxypropyl emthylcellulose 250g, polyacrylic resin 175g, micropowder silica gel 3g, magnesium stearate 3g and 120g water.
The method for preparing of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Form the various supplementary materials of preparation according to the supplementary material of above-mentioned Guanfacine Hydrochloride slow releasing tablet; The Guanfacine Hydrochloride 11.48g for preparing, lactose 232.5g, fumaric acid 75g, hydroxypropyl emthylcellulose 250g, polyacrylic resin 175g are pulverized, be crushed to, obtain uniformed powder through after in high-speed mixer, mixing 30 minutes behind 80 eye mesh screens; Adopt high-speed shearing machine under the high speed shear state, slowly to add binding agent water 120g the gained uniformed powder; High speed shear is granulated, and the gained granule was put into 60 ℃ of convection oven dry 2 hours, carries out uniformity of dosage units and water content inspection (dry back granule moisture content is no more than 5%); After qualified the gained granule is passed through 16 eye mesh screen granulate; Add fluidizer micropowder silica gel 3g and the magnesium stearate lubricant 3g for preparing behind the granulate, utilize mixer to continue to be mixed to mix homogeneously, at last according to the conventional method tabletting; Promptly get the Guanfacine Hydrochloride slow releasing tablet (with reference to 2010 editions two appendix X D of Chinese Pharmacopoeia and appendix X E; Every batch of testing product uniformity of dosage units and release degree are packed into after qualified in the lucifuge hermetic container, get product.）。
Embodiment 2: basic identical with embodiment 1, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.74g, mannitol 190g, citric acid 100g, hydroxypropyl cellulose 300g, polyacrylic resin 135g, micropowder silica gel 3g, sodium stearyl fumarate 5g and 5% polyvidone aqueous solution 100g.
Embodiment 3: basic identical with embodiment 1, difference is:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, lactose 200g, microcrystalline Cellulose 30g, fumaric acid 100g, ethyl cellulose 250g, polyacrylic resin 150g, micropowder silica gel 3g, magnesium stearate 3g and water 120g..
With prepared Guanfacine Hydrochloride slow releasing tablet among the embodiment 1 is specimen, and release degree experimental technique is following:
Get embodiment 1 products obtained therefrom,, adopt the dissolution determination subtraction unit according to drug release determination method (2010 editions two appendix X D of Chinese Pharmacopoeia, second method); Rotating speed is 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer 900ml of pH 2.2; Sampling time point is: 1 hour, 4 hours, 8 hours and 24 hours; It is an amount of to get solution at each time point, filters, and gets subsequent filtrate as need testing solution.Get the contrast solution and the need testing solution of concentration known, inject high performance liquid chromatograph respectively, the record chromatogram calculates different burst sizes constantly by external standard method.
Experimental result is seen the accompanying drawing 1 in the description of drawings, and embodiment 2,3 is under identical test condition, and experimental result is identical with embodiment 1, all meets the requirements.
Embodiment 4: basic identical with embodiment 1, difference is:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.48g, sucrose 175g, tartaric acid 50g, hydroxypropyl cellulose 200g, methylcellulose 115g, cellulose acetate phthalate ester 100g, vinyl acetate phthalate ester 47g, Pulvis Talci 5.25g, hydrogenated vegetable oil 5.25g and 50% ethanol water mixed solution 150g.
Embodiment 5: basic identical with embodiment 1, difference is:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 22.5g, starch 175g, Sargassum polysaccharides 100g, fumaric acid 62.5g, hydroxypropyl emthylcellulose 70g, carboxymethyl cellulose 50g, methylcellulose 30g, polyacrylic acid resin 120g, hydroxyethyl-cellulose acetyl cellulose 75g, hydrogenated vegetable oil 6.0g, Pulvis Talci 6.0g and 80% ethanol water mixed liquid 150g.
Embodiment 6: basic identical with embodiment 1, difference is:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～20 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.25g, malic acid 120g, succinic acid 67.5g, hydroxypropyl emthylcellulose 200g, carboxymethyl cellulose 137.5g, polyacrylic acid resin 120g, Hydroxypropyl Methyl Cellulose Phthalate 30g, micropowder silica gel 7.5g, magnesium stearate 7.5g and 95% ethanol water mixed liquid mixed liquor 180g.
With prepared Guanfacine Hydrochloride slow releasing tablet among the embodiment 1 is specimen, and release degree experimental technique is following:
Get embodiment 1 products obtained therefrom,, adopt the dissolution determination subtraction unit according to drug release determination method (2010 editions two appendix X D of Chinese Pharmacopoeia, second method); Rotating speed is 100rpm, and temperature is 37 ℃, and release medium is the hydrochloride buffer 900ml of pH 2.2; Sampling time point is: 1 hour, 4 hours, 8 hours and 24 hours; It is an amount of to get solution at each time point, filters, and gets subsequent filtrate as need testing solution.Get the contrast solution and the need testing solution of concentration known, inject high performance liquid chromatograph respectively, the record chromatogram calculates different burst sizes constantly by external standard method.
Experimental result is seen the accompanying drawing 1 in the description of drawings, and the products obtained therefrom of embodiment 2～6 is under identical test condition, and experimental result is identical with embodiment 1, all meets the requirements.
Embodiment 7:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 12.0g, lactose 200g, fumaric acid 100g, hydroxypropyl emthylcellulose 260g and polyacrylic resin 110g.
The method for preparing of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials; At first Guanfacine Hydrochloride, filler (lactose and fumaric acid), slow-release material (hydroxypropyl emthylcellulose) and pH sensitive material (polyacrylic resin) are imported in the high-speed mixer and mix; Obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain the granule of particle diameter less than 14 eye mesh screens; The gained granule is carried out drying; Be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule through the granule of 16 eye mesh screens.
Embodiment 8: basic identical with embodiment 7, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.6g, lactose 234g, hydroxypropyl emthylcellulose 234g and polyacrylic resin 196g.
Embodiment 9: basic identical with embodiment 7, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit; The shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 20.5g, fumaric acid 168g, hydroxypropyl emthylcellulose 300g and polyacrylic resin 180g.
Embodiment 10:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit, and the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 5.0g, fumaric acid 320g and hydroxypropyl emthylcellulose 280g.
The method for preparing of Guanfacine Hydrochloride slow releasing preparation of the present invention:
Supplementary material proportioning according to above-mentioned Guanfacine Hydrochloride slow releasing preparation is prepared various supplementary materials; At first Guanfacine Hydrochloride, filler (fumaric acid) and slow-release material (hydroxypropyl emthylcellulose) are imported in the high-speed mixer and mix; Obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain the granule of particle diameter less than 14 eye mesh screens; The gained granule is carried out drying; Be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule through the granule of 16 eye mesh screens.
Embodiment 11: basic identical with embodiment 10, difference is:
The supplementary material of Guanfacine Hydrochloride slow releasing preparation of the present invention consists of:
With g is unit, and the shared weight portion of each supplementary material in the Guanfacine Hydrochloride slow releasing preparation original formulation has been enlarged 5～15 times, and the supplementary material of Guanfacine Hydrochloride slow releasing tablet consists of Guanfacine Hydrochloride 11.5g, lactose 300g and hydroxypropyl emthylcellulose 260g.
Claims (10)
1. a Guanfacine Hydrochloride slow releasing preparation is characterized in that: represent that with weight portion said Guanfacine Hydrochloride slow releasing preparation contains 0.2～4 part of Guanfacine Hydrochloride in forming, 10～50 parts of 10～60 parts of filleies and slow-release materials.
2. Guanfacine Hydrochloride slow releasing preparation according to claim 1 is characterized in that: said Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming.
3. Guanfacine Hydrochloride slow releasing preparation according to claim 2 is characterized in that: said Guanfacine Hydrochloride slow releasing preparation contains 0.4～3 part of Guanfacine Hydrochloride in forming, 25～45 parts of filleies, 10～30 parts of 15～45 parts of slow-release materials and pH sensitive materials.
4. Guanfacine Hydrochloride slow releasing preparation according to claim 1 is characterized in that: said Guanfacine Hydrochloride slow releasing preparation also contains 1～40 part of pH sensitive material in forming, 0.1～1 part of fluidizer, 0.1～10 part of 0.1～1 part of lubricant and binding agent.
5. Guanfacine Hydrochloride slow releasing preparation according to claim 4; It is characterized in that: said Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride; 25～45 parts of filleies, 15～45 parts of slow-release materials, 10～30 parts of pH sensitive materials; 0.1～1 part of fluidizer, 0.1～1 part of lubricant and 0.1～10 part of composition of binding agent.
6. according to each described Guanfacine Hydrochloride slow releasing preparation of claim 1～5, it is characterized in that: said filler is any one or more in sucrose, lactose, mannitol, starch, microcrystalline Cellulose, Sargassum polysaccharides, citric acid, fumaric acid, tartaric acid, malic acid, succinic acid and the chitosan;
Said slow-release material is any or more than one in ethyl cellulose, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, carboxymethyl cellulose, methylcellulose, Palmic acid and the chitosan;
Said pH sensitive material is any or more than one in polyacrylic acid resin, hydroxyethyl-cellulose acetyl cellulose, cellulose acetate-phthalate ester, cellulose acetate phthalate ester, vinyl acetate phthalate ester, hydroxypropyl methyl cellulose phthalate, Lac and the Hydroxypropyl Methyl Cellulose Phthalate;
Said fluidizer is any one or more in magnesium stearate, Pulvis Talci, hydrogenated vegetable oil and the micropowder silica gel;
Said lubricant is any one or more in Pulvis Talci, hydrogenated vegetable oil, sodium stearyl fumarate, magnesium stearate and the stearyl alcohol;
Said binding agent is any or more than one in water, dehydrated alcohol, water and alcohol mixed solution, Gonak, hydroxypropyl cellulose solution, povidone solution and the carboxymethylcellulose sodium solution.
7. Guanfacine Hydrochloride slow releasing preparation according to claim 6 is characterized in that: said filler is any or two kinds in lactose and the fumaric acid; Said slow-release material is a hydroxypropyl emthylcellulose, and the methoxyl group substitute proportion is 15%～40% in the hydroxypropyl emthylcellulose, and the hydroxypropyl substitute proportion is 3%～15%; Said pH sensitive material is the polyacrylic acid resin; Said fluidizer is micropowder silica gel; Said lubricant is any or two kinds in magnesium stearate and the sodium stearyl fumarate; Said binding agent is water or water and alcohol mixed solution.
8. Guanfacine Hydrochloride slow releasing preparation according to claim 7; It is characterized in that: said Guanfacine Hydrochloride slow releasing preparation is by 0.4～3 part of raw material Guanfacine Hydrochloride, 10～40 parts of lactose, 0～20 part of fumaric acid; 10～50 parts of hydroxypropyl emthylcelluloses; 10～40 parts of polyacrylic resins, 0～1 part of micropowder silica gel, 0～1 part of magnesium stearate and 0～10 part of composition of water.
9. the method for preparing of a Guanfacine Hydrochloride slow releasing preparation is characterized in that, said method for preparing may further comprise the steps:
Supplementary material proportioning according to each said Guanfacine Hydrochloride slow releasing preparation of claim 1～3 is prepared various supplementary materials; At first with mixing in Guanfacine Hydrochloride, filler and slow-release material or Guanfacine Hydrochloride, filler, slow-release material and the pH sensitive material importing high-speed mixer; Obtain uniformed powder behind the mix homogeneously, adopt the high-speed shearing machine shear granulation then, obtain the granule of particle diameter less than 14 eye mesh screens; The gained granule is carried out drying; Be dried to gained granule water content and be no more than 5%, select and to obtain Guanfacine Hydrochloride slow releasing preparation granule through the granule of 16 eye mesh screens;
Perhaps prepare various supplementary materials according to the supplementary material proportioning of claim 4,5 or 8 each said Guanfacine Hydrochloride slow releasing preparation; At first Guanfacine Hydrochloride, filler, slow-release material and pH sensitive material are imported in the high-speed mixer and mix, obtain uniformed powder behind the mix homogeneously, add the binding agent for preparing then; Adopt the high-speed shearing machine shear granulation; Obtain the granule of particle diameter, the gained granule is carried out drying, be dried to gained granule water content and be no more than 5% less than 14 eye mesh screens; Selecting can be through the granule of 16 eye mesh screens; It is even to add the fluidizer and the mix lubricant that prepare then, at last according to the conventional method tabletting, processes the product Guanfacine Hydrochloride slow releasing tablet of all size.
10. the method for preparing of Guanfacine Hydrochloride slow releasing preparation according to claim 9 is characterized in that: the sheet of said product Guanfacine Hydrochloride slow releasing tablet heavily is 100～350mg; The effective dose of Guanfacine Hydrochloride is 0.5～5mg in the products obtained therefrom Guanfacine Hydrochloride slow releasing tablet.
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| CN 201210090024 CN102579381B (en) | 2012-03-30 | 2012-03-30 | Guanidine hydrochloride sustained release preparation and preparation method thereof |
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| CN 201210090024 CN102579381B (en) | 2012-03-30 | 2012-03-30 | Guanidine hydrochloride sustained release preparation and preparation method thereof |
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| CN102579381A true CN102579381A (en) | 2012-07-18 |
| CN102579381B CN102579381B (en) | 2013-07-10 |
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| CN 201210090024 Active CN102579381B (en) | 2012-03-30 | 2012-03-30 | Guanidine hydrochloride sustained release preparation and preparation method thereof |
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Cited By (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102887838A (en) * | 2012-10-29 | 2013-01-23 | 河南中帅医药科技发展有限公司 | Preparation method of guanfacine hydrochloride |
| CN103705480A (en) * | 2013-12-31 | 2014-04-09 | 郑州大明药物科技有限公司 | Guanfacine hydrochloride sustained-release preparation and preparation method thereof |
| CN104473906A (en) * | 2014-11-21 | 2015-04-01 | 哈尔滨圣吉药业股份有限公司 | Guanfacine hydrochloride sustained release pellets and preparation method thereof |
| CN104490982A (en) * | 2014-11-28 | 2015-04-08 | 普正药业股份有限公司 | Eucommia antihypertensive slow-release preparation and preparation method thereof |
| CN108042502A (en) * | 2017-12-05 | 2018-05-18 | 浙江华海药业股份有限公司 | A kind of guanfacine hydrochloride sustained release tablets and preparation method thereof |
| US10723700B2 (en) | 2015-08-12 | 2020-07-28 | Incyte Corporation | Salts of an LSD1 inhibitor |
| US10800779B2 (en) | 2015-04-03 | 2020-10-13 | Incyte Corporation | Heterocyclic compounds as LSD1 inhibitors |
| US10968221B2 (en) | 2014-07-10 | 2021-04-06 | Incyte Corporation | Substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors |
| US10968200B2 (en) | 2018-08-31 | 2021-04-06 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| US11155532B2 (en) | 2014-02-13 | 2021-10-26 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| CN113648285A (en) * | 2021-07-15 | 2021-11-16 | 南京海纳医药科技股份有限公司 | Guanfacine hydrochloride membrane controlled-release tablet and preparation method thereof |
| US11247992B2 (en) | 2014-02-13 | 2022-02-15 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| EP4292586A1 (en) * | 2022-06-15 | 2023-12-20 | Sawai Pharmaceutical Co., Ltd. | Guanfacine hydrochloride containing pharmaceutical preparation |
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| CN101252917A (en) * | 2005-07-28 | 2008-08-27 | 夏尔有限责任公司 | Pharmaceutical formulations/composition of guanfacine suitable for single dose form administration daily |
| CN101588794A (en) * | 2007-01-25 | 2009-11-25 | 万能药生物有限公司 | Modified release pharmaceutical composition and a process of making the same |
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| CN101252917A (en) * | 2005-07-28 | 2008-08-27 | 夏尔有限责任公司 | Pharmaceutical formulations/composition of guanfacine suitable for single dose form administration daily |
| CN101588794A (en) * | 2007-01-25 | 2009-11-25 | 万能药生物有限公司 | Modified release pharmaceutical composition and a process of making the same |
Cited By (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102887838A (en) * | 2012-10-29 | 2013-01-23 | 河南中帅医药科技发展有限公司 | Preparation method of guanfacine hydrochloride |
| CN103705480A (en) * | 2013-12-31 | 2014-04-09 | 郑州大明药物科技有限公司 | Guanfacine hydrochloride sustained-release preparation and preparation method thereof |
| US11247992B2 (en) | 2014-02-13 | 2022-02-15 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| US11155532B2 (en) | 2014-02-13 | 2021-10-26 | Incyte Corporation | Cyclopropylamines as LSD1 inhibitors |
| US10968221B2 (en) | 2014-07-10 | 2021-04-06 | Incyte Corporation | Substituted [1,2,4]triazolo[1,5-a]pyrazines as LSD1 inhibitors |
| CN104473906A (en) * | 2014-11-21 | 2015-04-01 | 哈尔滨圣吉药业股份有限公司 | Guanfacine hydrochloride sustained release pellets and preparation method thereof |
| CN104490982A (en) * | 2014-11-28 | 2015-04-08 | 普正药业股份有限公司 | Eucommia antihypertensive slow-release preparation and preparation method thereof |
| US10800779B2 (en) | 2015-04-03 | 2020-10-13 | Incyte Corporation | Heterocyclic compounds as LSD1 inhibitors |
| US11401272B2 (en) | 2015-04-03 | 2022-08-02 | Incyte Corporation | Heterocyclic compounds as LSD1 inhibitors |
| US10723700B2 (en) | 2015-08-12 | 2020-07-28 | Incyte Corporation | Salts of an LSD1 inhibitor |
| US11498900B2 (en) | 2015-08-12 | 2022-11-15 | Incyte Corporation | Salts of an LSD1 inhibitor |
| CN108042502A (en) * | 2017-12-05 | 2018-05-18 | 浙江华海药业股份有限公司 | A kind of guanfacine hydrochloride sustained release tablets and preparation method thereof |
| US10968200B2 (en) | 2018-08-31 | 2021-04-06 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| US11512064B2 (en) | 2018-08-31 | 2022-11-29 | Incyte Corporation | Salts of an LSD1 inhibitor and processes for preparing the same |
| CN113648285A (en) * | 2021-07-15 | 2021-11-16 | 南京海纳医药科技股份有限公司 | Guanfacine hydrochloride membrane controlled-release tablet and preparation method thereof |
| EP4292586A1 (en) * | 2022-06-15 | 2023-12-20 | Sawai Pharmaceutical Co., Ltd. | Guanfacine hydrochloride containing pharmaceutical preparation |
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