CN100493512C - Slow-released preparation containing hydrochlorothiazide and clonidine hydrochloride and its preparing method - Google Patents
Slow-released preparation containing hydrochlorothiazide and clonidine hydrochloride and its preparing method Download PDFInfo
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- CN100493512C CN100493512C CNB2007100203078A CN200710020307A CN100493512C CN 100493512 C CN100493512 C CN 100493512C CN B2007100203078 A CNB2007100203078 A CN B2007100203078A CN 200710020307 A CN200710020307 A CN 200710020307A CN 100493512 C CN100493512 C CN 100493512C
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Abstract
The present invention belongs to the field of medicine preparation. In the concrete, it relates to a compound medicine slow release preparation containing hydrochlorothiazide and clonidine hydrochloride. It is characterized by that said slow release preparation is composed of two portions of quick-released portion and slow-released portion. Besides, said invention also provides its preparation method and concrete steps.
Description
Technical field
The present invention relates to field of pharmaceutical preparations, be specifically related to the slow releasing preparation of hydrochlorothiazide and clonidine hydrochloride compound medicine, the invention also discloses the preparation method of this slow releasing preparation.
Background technology
Hydrochlorothiazide is a kind of diuretic, and the medication initial stage is a natriuretic diuretic, and blood volume and extracellular fluid are reduced, and cardiac output reduces, blood pressure drops.Continuous use is after several weeks, blood volume and cardiac output recover gradually, blood pressure still continues to reduce, the negative booster of this moment is made as the natriuretic diuretic effect, the content of sodium ion in the arterial wall cell is descended, reduce the reactivity of vascular smooth muscle, Peripheral resistance is descended, induce arterial wall to produce simultaneously and expand angiogenic substance the endogenous vaso-active substance.Can be used for treating mild hypertension, also can be used as basic depressor, share, treatment moderate, severe hypertension with other depressor.Clonidine hydrochloride is a kind of maincenter depressor, its mechanism of action is by the exciting medulla oblongata nucleus solitarius time neuronic postsynaptic membrane alpha-2 receptor of one-level, the periphery sympathetic nerve is suppressed, causes that decreased heart rate, cardiac output decline, vasodilation, Peripheral resistance descend blood pressure drops.Two medication combined medication treatment hypertension, can produce good synergy, this compound preparation changes hypertensive patient's cardiovascular beneficial effect, as reduce left ventricular hypertrophy, alleviate vascular hypertrophy, reduce albuminuria, reduce peripheral vascular resistance, keep kidney blood vessel kinetics function etc., can also offset untoward reaction and reduce side effect.
Hydrochlorothiazide is a fat-soluble medicine, absorbs well, and part combines with plasma protein, and the half-life is 6-15h.Clonidine hydrochloride is a water soluble drug, good absorbing, and the bioavailability height, the half-life is 7.4-13h.Used clinically hydrochlorothiazide clonidine hydrochloride compound preparation is an ordinary tablet at present, three times on the one.Conventional tablet is owing to exist release too fast, and instant blood drug level is too high, and blood drug level is low excessively again after of short duration metabolism, and the former easily produces toxic and side effects, and the latter can make duration of efficacy too short.Patient needed take more than three times in one in addition, and is extremely inconvenient, easily forgets clothes and misses, and curative effect is exerted an influence.
Summary of the invention
The invention discloses the slow releasing preparation of a kind of hydrochlorothiazide and clonidine hydrochloride compound medicine.Can reach medicine and steadily discharge, blood drug level can maintain fluctuation in the very little scope, has the minimizing administration number of times, and it is steady to take back blood drug level, and toxic and side effects is little, takes characteristics such as safety, reduces administration number of times simultaneously, improves hyperpietic's compliance.
Because there are certain difference in the physicochemical property and the characteristics of pharmacokinetics of hydrochlorothiazide and clonidine hydrochloride, therefore, compound slow release preparation of the present invention is made up of rapid release and slow release two parts, after medicine enters in the body like this, immediate release section discharges rapidly, reaches certain blood drug level, the slow-released part slow release, keep certain blood drug level, play the effect of steady blood pressure lowering.
Slow releasing preparation of the present invention, wherein immediate release section contains hydrochlorothiazide 3-7.5mg, and slow-released part contains hydrochlorothiazide 10-40mg and clonidine hydrochloride 0.0375-0.15mg.
Above-mentioned slow releasing preparation can be mixed with into dosage forms such as slow releasing tablet, granule or micropill with hydrochlorothiazide with preparation technique pharmaceutically commonly used with clonidine hydrochloride and slow-release material, and then contains the immediate release section of hydrochlorothiazide in micropill or tablet outer wrapping.Also immediate release section is prepared into granule, sheet or micropill, partially mixed with slow release then, in incapsulating.
Because the physicochemical property of hydrochlorothiazide and clonidine hydrochloride is different with releasing properties, slow-released part mixes after preferably hydrochlorothiazide and clonidine hydrochloride being prepared into after the dosage forms such as slow release slow-releasing granules, slow-release micro-pill or slow release small pieces respectively more by a certain percentage, and then mix with the hydrochlorothiazide immediate release section, the hydrochlorothiazide immediate release section can be prepared into fast-release tablet, micropill or granule etc.Preferably with in incapsulating after slow-released part and the immediate release section mixing.
According to different drug release behavior of two medicines and clinical treatment effective dose, the preferred slow release hydrochlorothiazide of the present invention partly contains other pharmaceutic adjuvant of 40～60% hydrochlorothiazide, 10～35% slow-release materials and surplus.Preferred slow release clonidine hydrochloride partly contains other pharmaceutic adjuvant of 0.1～0.3% clonidine hydrochloride, 50～95% slow-release materials and surplus.
In above-mentioned slow-release material preference card POP, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, Cera Flava, stearic acid, glyceryl monostearate, octadecanol, polyethylene, polypropylene, polysiloxanes, inertia waxiness, the acrylic resin one or more.Further preference card POP and/or hydroxypropyl methylcellulose.More preferably carbopol and hydroxypropyl methylcellulose.
Above-mentioned other pharmaceutic adjuvant is one or more in filler, disintegrating agent, binding agent, lubricant preferably.
The rapid release hydrochlorothiazide contains hydrochlorothiazide and other pharmaceutic adjuvant.The adjuvant of using always on these adjuvant galenic pharmacies.As: filler, disintegrating agent, binding agent, lubricant etc.
In the preferred lactose of above-mentioned filler, sucrose, starch, pregelatinized Starch, cellulose, Icing Sugar, dextrin, glucose, mannitol, calcium sulfate, the calcium bicarbonate one or more; In the preferred carboxymethyl starch sodium of disintegrating agent, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, the cross-linking sodium carboxymethyl cellulose one or more; In binding agent preferred water, alcohol, polyvinylpyrrolidone, starch slurry, the rubber cement one or more; In the preferred magnesium stearate of lubricant, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or the magnesium one or more.
More have the dosage of choosing to be: immediate release section contains hydrochlorothiazide 6mg, and slow-released part contains hydrochlorothiazide 31.5mg and clonidine hydrochloride 0.1125mg.
Slow releasing preparation of the present invention has changed the single release form of original treatment hypertension drug, and rapid release and slow release are organically combined, and can produce hypotensive effect rapidly and keep the long period in the regular hour.The present invention discharged 15-30% in first hour, can produce hypotensive effect at once, discharged in two kinds of medicine 2-24h afterwards of remainder, thereby produced the antihypertensive effect that continues.The invention provides a kind of drug reservoir form, make and contain the antihypertensive medicine of hydrochlorothiazide and clonidine or other and can slowly discharge.
Slow releasing preparation preparation method of the present invention is simple, to be prepared into small pieces is example, preparation method comprises: with hydrochlorothiazide and clonidine hydrochloride respectively with auxiliary materials and mixing after, directly or after making granule be pressed into hydrochlorothiazide slow release small pieces and clonidine hydrochloride slow release small pieces by powder; Prepare hydrochlorothiazide rapid release small pieces more according to a conventional method.To be poured in the same capsule after slow release and the mixing of rapid release small pieces, preparation becomes compound slow release preparation of the present invention.
The hydrochlorothiazide and the clonidine hydrochloride compound preparation that make according to technical scheme of the present invention, oral back runs into Digestive system in gastrointestinal tract, hydrochlorothiazide and clonidine hydrochloride slowly discharge, and can keep long antihypertensive effect, thereby having reduced administration number of times, patient's compliance improves.The relative ordinary preparation of blood drug level is steady in the body of this compound slow release preparation, therefore, can reduce the toxic and side effects that causes more greatly because of the blood concentration fluctuation.
Compound slow release preparation of the present invention has the characteristic of the slow release of 24h in water, 0.1NHCl, pH6.8 buffer (pressing the configuration of Chinese Pharmacopoeia method) or mimic physiological environment (2-3h in the simulated gastric fluid changes simulated intestinal fluid then over to).
In the hydrochlorothiazide is to discharge index:
Time (h) accumulative total discharges %
1 15-30％
4 30-60％
8 60-90％
12 80-100％
In the clonidine hydrochloride is to discharge index:
Time (h) accumulative total discharges %
1 15-30％
4 30-60％
8 70-90％
12 85-100％
Slow releasing preparation of the present invention not only in dissolution in vitro test release profiles reached slow release effect, also confirmed this slow release effect in the test in animal body.
The specific embodiment
Embodiment 1
Below be by 1000 used amounts
A. hydrochlorothiazide rapid release small pieces
Amounts of components (g)
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components (g)
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose 12.5
Carbopol 2
Lactose 8.725
Magnesium stearate 0.275
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose 25
Carbopol 2.5
Lactose 22.1375
Magnesium stearate 0.25
Preparation technology is as follows:
The supplementary material crushing screening is behind above-mentioned recipe quantity difference mixing, then with mix lubricant.Be pressed into small pieces respectively, be poured in the capsule after the mixing.
Embodiment 2
The consumption of present embodiment is by 1000 used amounts
A. hydrochlorothiazide rapid release small pieces
Amounts of components
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components (g)
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose K100 10.2
Carbopol 9.6
Lactose 19.2
Magnesium stearate 0.3
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose K100 30
Carbopol 9
Lactose 10.6375
Magnesium stearate 0.25
Preparation method is with embodiment 1.
Embodiment 3
The consumption of present embodiment is by 1000 used amounts
A. hydrochlorothiazide rapid release small pieces
Amounts of components
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose K15 7.8
Carbopol 1.2
Lactose 19.2
Magnesium stearate 0.3
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose K15 36
Carbopol 21
Lactose 2.5875
Magnesium stearate 0.3
Preparation method is with embodiment 1.
Embodiment 4
A. hydrochlorothiazide rapid release small pieces
Amounts of components
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose K15 3.6
Carbopol 4.8
Lactose 19.8
Magnesium stearate 0.3
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose K15 36
Carbopol 12
Ethyl cellulose 6
Lactose 5.5875
Magnesium stearate 0.3
Preparation method is with embodiment 1.
Embodiment 5
A. hydrochlorothiazide rapid release small pieces
Amounts of components
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose K15 10.8
Carbopol 2.4
Lactose 15
Magnesium stearate 0.3
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose K15 36
Carbopol 12
Stearic acid 7.2
Lactose 4.3875
Magnesium stearate 0.3
Preparation method is with embodiment 1.
Embodiment 6
A. hydrochlorothiazide rapid release small pieces
Amounts of components
Hydrochlorothiazide 6
Microcrystalline Cellulose 10
Lactose 12.95
Polyvinylpolypyrrolidone 0.9
Magnesium stearate 0.15
B. hydrochlorothiazide slow release small pieces
Amounts of components
Hydrochlorothiazide 31.5
Hydroxypropyl emthylcellulose K15 13.2
Carbopol 1.2
Lactose 13.8
Magnesium stearate 0.3
C. clonidine hydrochloride slow release small pieces
Amounts of components
Clonidine hydrochloride 0.1125
Hydroxypropyl emthylcellulose K15 36
Carbopol 12
Waxiness 888 6
Lactose 5.5875
Magnesium stearate 0.3
Preparation method is with embodiment 1.
Embodiment 7
The medicine dissolution test
Adopt the cuvette oar method in the Chinese Pharmacopoeia 2005 editions, 75 rev/mins, distilled water or 0.1NHCl150ml are dissolution medium, and the slow releasing preparation experiment stripping result of embodiment 1～6 is as follows
Table 1 dissolution data
Table 2 dissolution data
Embodiment 8
The pharmacokinetics experiment:
Contrast medicine: hydrochlorothiazide tablet, specification 25mg sheet
The clonidine hydrochloride sheet, specification 75 μ g/ sheets
Animal: beagle dog
Instrument and reagent: Finnigan TSQ DISCOVER MAX LC-MS instrument (Thermo company); The XS105 electronic balance, prunus mume (sieb.) sieb.et zucc. Teller-holder benefit instrument (Shanghai) Co., Ltd.; Methanol (MERCK company) chromatographically pure; Ether (Shanghai Prospirolboli joannsi chemical reagent work)
Experimental technique
Select 6 of healthy adult beagle dogs for use, body weight 8-10kg.Be divided into two groups immediately, adopt binary cycle dual crossing conceptual design, take contrast medicine (3 of hydrochlorothiazide tablets, 2 of clonidine hydrochloride sheets) and test preparation (2) respectively.Taking dose is hydrochlorothiazide 75mg, clonidine hydrochloride 225 μ g.Tight food spent the night before the beagle dog was taken medicine, and is from hind leg venous blood collection 3ml, centrifugal in take medicine back 0,0.25,0.50,0.75,1,2,3,4,5,6,7,8,10,12,24,36h, gets blood plasma in-20 ℃ of storages, is used for blood drug level and detects.
Testing result is as follows:
Table 3 hydrochlorothiazide animal experiment testing result
A is the test preparation of the embodiment of the invention 1～3, and R is the reference preparation hydrochlorothiazide tablet.
By table 3 as seen, hydrochlorothiazide half-life (T in the slow releasing preparation of the present invention
1/2) obviously prolong medicine peak time (T than common hydrochlorothiazide tablet
Max) also prolong maximum plasma concentration (C
Max) descend much than hydrochlorothiazide tablet, really reached effect steady, long-acting release.
Table 4 clonidine animal experiment testing result
A is the test preparation of the embodiment of the invention 1～3, and R is a reference preparation clonidine hydrochloride sheet.
By table 4 as seen, clonidine hydrochloride half-life (T in the slow releasing preparation of the present invention
1/2) obviously prolong medicine peak time (T than common clonidine hydrochloride sheet
Max) also prolong maximum plasma concentration (C
Max) descend much than clonidine hydrochloride sheet, really reached effect steady, long-acting release.
Claims (9)
1, a kind of slow releasing preparation that contains hydrochlorothiazide and clonidine hydrochloride, it is characterized in that forming by rapid release and slow release two parts, wherein per unit preparation immediate release section contains hydrochlorothiazide 3-7.5mg, slow-released part contains hydrochlorothiazide 10-40mg and clonidine hydrochloride 0.0375-0.15mg, and remix formed after slow-released part was made slow-releasing granules, slow-release micro-pill or slow release small pieces by hydrochlorothiazide and clonidine hydrochloride respectively.
2, the slow releasing preparation of claim 1, wherein the slow release hydrochlorothiazide partly contains other pharmaceutic adjuvant of 40～60% hydrochlorothiazide, 10～35% slow-release materials and surplus.
3, the slow releasing preparation of claim 1, wherein the slow release clonidine hydrochloride partly contains other pharmaceutic adjuvant of 0.1～0.3% clonidine hydrochloride, 50～95% slow-release materials and surplus.
4, claim 2 or 3 slow releasing preparation, wherein slow-release material is selected from one or more in carbopol, ethyl cellulose, methylcellulose, hydroxypropyl cellulose, hydroxypropyl methylcellulose, carboxymethyl cellulose, stearic acid, glyceryl monostearate, octadecanol, polyethylene, polypropylene, polysiloxanes, inertia waxiness, the acrylic resin.
5, the slow releasing preparation of claim 4, wherein slow-release material is carbopol and/or hydroxypropyl methylcellulose.
6, the slow releasing preparation of claim 1, wherein the rapid release hydrochlorothiazide partly contains hydrochlorothiazide and other pharmaceutic adjuvant.
7, claim 2,3 or 6 slow releasing preparation, wherein other pharmaceutic adjuvant is selected from one or more in filler, disintegrating agent, binding agent, the lubricant.
8, the slow releasing preparation of claim 7, wherein filler is selected from one or more in lactose, sucrose, starch, pregelatinized Starch, cellulose, Icing Sugar, dextrin, glucose, mannitol, calcium sulfate, the calcium bicarbonate; Disintegrating agent is selected from one or more in carboxymethyl starch sodium, low-substituted hydroxypropyl cellulose, polyvinylpolypyrrolidone, the cross-linking sodium carboxymethyl cellulose; Binding agent is selected from one or more in water, alcohol, polyvinylpyrrolidone, starch slurry, the rubber cement; Lubricant is selected from one or more in magnesium stearate, Pulvis Talci, micropowder silica gel, sodium lauryl sulphate or the magnesium.
9, the slow releasing preparation of claim 1, wherein per unit preparation immediate release section contains hydrochlorothiazide 6mg, and slow-released part contains hydrochlorothiazide 31.5mg and clonidine hydrochloride 0.1125mg.
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| Application Number | Priority Date | Filing Date | Title |
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| CNB2007100203078A CN100493512C (en) | 2007-02-12 | 2007-02-12 | Slow-released preparation containing hydrochlorothiazide and clonidine hydrochloride and its preparing method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2007100203078A CN100493512C (en) | 2007-02-12 | 2007-02-12 | Slow-released preparation containing hydrochlorothiazide and clonidine hydrochloride and its preparing method |
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| CN101023951A CN101023951A (en) | 2007-08-29 |
| CN100493512C true CN100493512C (en) | 2009-06-03 |
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Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104352473A (en) * | 2014-11-21 | 2015-02-18 | 哈尔滨圣吉药业股份有限公司 | Clonidine hydrochloride sustained release tablets and preparation method thereof |
| CN109288836B (en) * | 2018-10-17 | 2021-02-05 | 常州制药厂有限公司 | Compound dihydralazine sulfate preparation as well as preparation method and application thereof |
| CN109260168B (en) * | 2018-11-30 | 2020-10-16 | 正大制药（青岛）有限公司 | Clonidine hydrochloride sustained release tablet |
| CN112043677A (en) * | 2020-09-17 | 2020-12-08 | 山东大学 | Clonidine hydrochloride sustained-release micro-tablets and preparation method and application thereof |
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2007
- 2007-02-12 CN CNB2007100203078A patent/CN100493512C/en active Active
Non-Patent Citations (4)
| Title |
|---|
| HPLC法测定常药降压片中两组分的含量. 廖斌等.中国药科大学学报，第34卷第1期. 2003 |
| HPLC法测定常药降压片中两组分的含量. 廖斌等.中国药科大学学报，第34卷第1期. 2003 * |
| 氢氯噻嗪缓释片的制备及体外释放考察. 贺国芳等.中国医院药学杂志，第24卷第9期. 2004 |
| 氢氯噻嗪缓释片的制备及体外释放考察. 贺国芳等.中国医院药学杂志，第24卷第9期. 2004 * |
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Effective date of registration: 20210210 Address after: 102600 Room 301, 3 / F, building 2, courtyard 5, Tianhua street, Daxing biomedical industry base, Zhongguancun Science and Technology Park, Daxing District, Beijing Patentee after: Beijing Heyuan Huifeng Pharmaceutical Technology Co.,Ltd. Address before: 230088 room c-204, National University Science Park, 602 Huangshan Road, Hefei City, Anhui Province Patentee before: HEFEI COSOURCE MEDICINE TECHNOLOGY Co.,Ltd. |