CN1931166A - Hypertension treating medicine - Google Patents
Hypertension treating medicine Download PDFInfo
- Publication number
- CN1931166A CN1931166A CN 200610015691 CN200610015691A CN1931166A CN 1931166 A CN1931166 A CN 1931166A CN 200610015691 CN200610015691 CN 200610015691 CN 200610015691 A CN200610015691 A CN 200610015691A CN 1931166 A CN1931166 A CN 1931166A
- Authority
- CN
- China
- Prior art keywords
- aranidipine
- solution
- acrylic resin
- prescription
- tablet
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The present invention discloses one kind of hypertension-treating enteric coated aranidipine tablet with aranidipine as effective component. The core of the coated tablet is prepared with aranidipine, acrylic resin L100, acrylic resin S100, lactose, starch, microcrystalline cellulose, hydroxypropyl methyl cellulose and magnesium stearate as material. The enteric coated aranidipine tablet has high bioavailability, lasting effect, high patient's compliance and high curative effect on hypertension.
Description
Technical field
The present invention relates to the chemical drugs technical field, particularly relating to a kind of is effective ingredient preparation treatment hypertension enteric coatel tablets (trade names: the aranidipine enteric coatel tablets) with the aranidipine.
Background technology
Aranidipine, its chemical structural formula is:
Molecular formula: C
19H
20N
2ON
2O
7
Molecular weight: 388.37
Chemical name: (±) 1,4-dihydro-2,6-dimethyl-4-(2-nitrobenzophenone)-3,5-dipicolinic acid methyl-2-oxygen propyl diester
Aranidipine is got permission for Japanese roc (Taiho) pharmaceutical industries Co., Ltd. (world's new drug development present situation calendar year 2001 9 pages) exploitation and in 1996 in early days first at Japan's listing (new drug 1999 the 47th phase 185 pages) recently, go on the market in the U.S. in succession, according to the literature, multicenter, the double-blind trial that carries out in Japan shows takes the aranidipine effective percentage: 413 routine hyperpietic's total effective rates are 89.1% (368 examples/413 examples), and various indication effective percentage are as follows respectively:
| Indication | Effective percentage |
| Gently, moderate essential hypertension | 90.9% (314 examples/349 examples) |
| Severe hypertension | 88.9% (32 examples/36 examples) |
| Hypertension with renal function injury | 78.6% (22 examples/28 examples) |
Take for a long time and show that antihypertensive effect is good, effective percentage is 88.3% (53 examples/60 examples); Every day is once oral, be a hypertensive vasodilator of treatment and calcium channel blocker, curative effect height, toleration are good, be a kind of potent, long-acting calcium antagonist, its action intensity and acting duration are all greater than nifedipine and nicardipine, and do not influence heart rate (Pharma projects in JIUYUE, 2002), also have the activity of open potassium channel.Clinical have curative effect preferably to essential hypertension, reduces peripheral vascular resistance, and cardiac hypertrophy is controlled, and penetrates the blood increased functionality.
This product is a new calcium antagonist.Its characteristics are:
1. have L type and T type calcium channel blocking action concurrently.Aranidipine blocks L type Ca with voltage and frequency dependence mode
2+Passage, and, have slower dynamics because aranidipine is higher to the affinity of the calcium channel of activation and inactivated state, therefore can long-acting vasodilator.In addition, also has the potassium channels opening effect.
2. aranidipine can obviously suppress the booster reaction that norepinephrine and periphery sympathetic stimulation cause, and should effect potent with it antihypertensive active is closely related.
3. aranidipine can also reduce the incidence rate of apoplexy, cardiac fibrosis, the arteriolitis of hypertrophy fiber-like and malignant nephrosclerosis.
Hypertension is commonly encountered diseases, China's generaI investigation in 1999 sickness rate 10%, 100,000,000 hyperpietics are arranged at present approximately, hypertension be again coronary heart disease, apoplexy, cardiorenal function depletion main diseases because of, China's human mortality's causal investigation statistics first shows, the cardiovascular diseases occupies first, and hypertension is its main hazard factor.So the control of hypertension is the research topic that the whole world is paid close attention to.
The aranidipine granule is Japan's listing product at present, this product is that Japanese roc medicine, ball pharmacy, BMS three companies are succeeded in developing on the calcium antagonist class medicine of bihydropyridine type, its trade name roc company is the Sapresta granule, and a ball and BMS company are the Bec granule.
Aranidipine has the bioavailability height, onset is slow, effect is lasting, and day clothes once, and are easy to use, improve patient's compliance greatly, are used for the treatment of hypertension curative effect preferably, and therefore needing the exploitation novel form is the new drug of a resisting hypertension system of domestic increase.
The compositions that discloses a kind of oral colon positioning feed among the application number 3120970.X on November 19 2003 applying date " application of medicine for stomach dynamic in preparation conlon targeting pharmaceutical composition " is arranged in addition, it comprises enteric coatel tablets, this sheet is divided into label and enteric coating liquid, label comprises ingredient, lactose, microcrystalline Cellulose, starch, magnesium stearate etc., and enteric coating liquid comprises Youteqi L (that is: acrylic resin L), Youteqi S (that is: acrylic resin S) etc.
" The 2nd Army Medical College journal " the 20th volume the 7th phase 455-458 page or leaf discloses the Licardipine Hydrochloride enteric sustained-release pellet, and it adopts acrylic resin to be positioned intestinal, and comprises adjuvants such as PEG6000, starch, sugar and dextrin.
Summary of the invention
The objective of the invention is to develop aranidipine enteric coatel tablets and preparation method thereof, provide treatment hypertensive new drug.
In order to reach purpose of the present invention, the technical scheme that the present invention takes is as follows: we carry out the prescription screening test and therefrom select prescription preferably with reference to external product, see: the research of aranidipine enteric coatel tablets prescription and technology:
Trade name: aranidipine enteric coatel tablets
English name: Aranidipine Enteric-coated Tablets
Material name: aranidipine
1. raw material sources Tianjin Inst. of Materia Medica chemical pharmacy portion lot number: 030222
2. write out a prescription
1) label (1000):
Aranidipine 5g
Acrylic resin (Eudragit L100) 20g
Acrylic resin (Eudragit S100) 5g
Lactose 80g
Starch 80g
Microcrystalline Cellulose 10g
Hydroxypropyl emthylcellulose (HPMC5cps) 10g
Magnesium stearate 1g
Make 1000 211g
2) enteric coating liquid prescription:
Acrylic resin (Eudragit L100) 10g
Polyethylene glycol 6000 1g
Pulvis Talci 2g
Titanium dioxide 2g
85% ethanol 200mL
Pigment is an amount of
Coating weightening finish 4～6%
3. preparation technology's (lucifuge operation)
1) tablet producing technology
A. adjuvant is crossed 100 mesh sieves.
B. aranidipine 5g, Eudragit E udragit L100 25g are dissolved in the 500ml80% alcoholic solution, are made into A solution.
C. aranidipine 5g, Eudragit E udragit S100 25g are dissolved in the 500ml80% alcoholic solution, are made into B solution.
D. take by weighing two parts of mixed accessories, every part contains lactose 80g, starch 80g, crystallite 10g, crosses 40 mesh sieve mixings.
E. a copy of it mixed accessories being packed in the fluid bed, is binding agent with A solution, and marumerization is granulated, and obtains granule A.
F. another part mixed accessories being packed in the fluid bed, is binding agent with B solution, and marumerization is granulated, and obtains granule B.
G.24 the order granulate is pressed the label prescription, and (granule A: granule B=80: 20) mixing adds hydroxypropyl emthylcellulose and magnesium stearate, with the abundant mixing of hybrid particles in proportion with two kinds of granules.
H. use 9 millimeters scrobicula drifts of φ tabletting on single punch tablet machine.
2) tablet coating technology
Eudragit E udragit L100 powder is with an amount of 85% ethanol swelling, and placement is spent the night, ultrasonic abundant dissolving, add polyethylene glycol 6000, add 85% ethanol to full dose after stirring evenly dissolving, add Pulvis Talci, titanium dioxide and pigment and cross colloid mill 5～6 times, after 120 mesh sieves, standby.
Tablet coating is to 4～6%, 40 ℃ of dry 2h of label weightening finish.Taking-up room temperature packing.
4. dosage form selection foundation
Aranidipine is the exploitation of Japanese Taiho Pharmaceutical Co. Ltd and got permission the listing in Japan first in 1996, is used for the treatment of hypertension.This product has the bioavailability height, acts on characteristics such as lasting.Oral, once-a-day, one time one bag.External product is a granule, and its specification is the 5mg/ bag.Because dosage is less, we are made into and are easy to take, tablet easy to carry, and with reference to external product the dosage of aranidipine enteric coatel tablets are decided to be the 5mg/ sheet.
5. prescription screening foundation
Weight and dosage with reference to the Japanese granule that goes on the market, in conjunction with China's pharmaceutic adjuvant situation, be optimized prescription, according to experience in the past, we have selected lactose, microcrystalline Cellulose, low-substituted hydroxypropyl cellulose, starch and sodium lauryl sulphate (SDS) to carry out the investigation of prescription and technology in test, with 40 minutes dissolution result of the test screening prescriptions, therefrom select prescription preferably, test recipe sees the following form:
The result of design prescription test is as follows:
Prescription I with ethanol system soft material, granulates aranidipine and adjuvant mix homogeneously with 20 mesh sieves, drying adds magnesium stearate, the compressed tablet heart, and tablet is loose, and hardness is not enough.
Prescription II is with aranidipine and adjuvant mix homogeneously, with 15%PVP (K
30) alcoholic solution system soft material, to granulate with 20 mesh sieves, drying adds magnesium stearate, the compressed tablet heart, disintegrate in 10 minutes.
Prescription III is with aranidipine raw material and SDS mixing, with all the other adjuvant mix homogeneously in the prescription, with 5%PVP (K
30) alcoholic solution system soft material, to granulate with 20 mesh sieves, drying adds magnesium stearate, behind the mixing, dashes the nail compressed tablet heart with 7 millimeters scrobiculas of φ on single punch tablet machine.Survey dissolution: oar method, 1. 100 rev/mins, in the stripping 65% in 40 minutes of 0.1mol/L acetum, 2. 100 rev/mins,, think that this prescription does not reach designing requirement in the stripping 51% in 40 minutes of 0.1mol/L hydrochloric acid solution.
Prescription IV with all the other adjuvant mix homogeneously in the prescription, with 5% starch slurry system soft material, granulates aranidipine and SDS mixing with 20 mesh sieves, drying adds magnesium stearate, behind the mixing, dashes the nail compressed tablet heart with 7 millimeters scrobiculas of φ on single punch tablet machine.Survey dissolution: oar method, 50 rev/mins, at 0.2% sodium lauryl sulphate (SDS) 500ml solution, stripping 78% in 40 minutes, thought that this prescription is hopeful to reach designing requirement.
Prescription V with all the other adjuvant mix homogeneously in the prescription, with 5%PVP alcoholic solution system soft material, granulates aranidipine and SDS mixing with 20 mesh sieves, drying adds magnesium stearate, behind the mixing, dashes the nail compressed tablet heart with 7 millimeters scrobiculas of φ on single punch tablet machine.Survey dissolution: oar method, 50 rev/mins, 1. at 0.2% sodium lauryl sulphate 500ml solution, stripping 77.4% in 40 minutes.2. at 0.4% sodium lauryl sulphate 500ml solution, stripping 90.3% in 40 minutes.3. at 0.6% sodium lauryl sulphate 500ml solution, stripping 92.1% in 40 minutes, thought that this prescription is hopeful to reach designing requirement.
Prescription VI with all the other adjuvant mix homogeneously in the prescription, with 5%PVP alcoholic solution system soft material, granulates aranidipine, lactose and SDS mixing with 20 mesh sieves, drying adds magnesium stearate, behind the mixing, dashes the nail compressed tablet heart with 7 millimeters scrobiculas of φ on single punch tablet machine.Survey dissolution: the oar method, be dissolution medium at 0.4% sodium lauryl sulphate 500ml, 1. 50 rev/mins, stripping 93.9% in 40 minutes, 2. 75 rev/mins, stripping 99.2% in 40 minutes, 3. 100 rev/mins, stripping 100.3% in 40 minutes, adjuvant is noiseless to ultraviolet determination, detects wavelength and determines at 239 places, thinks that the stripping of this prescription is very fast.
Prescription VII is with aranidipine, lactose and SDS mixing, with all the other adjuvant mix homogeneously in the prescription, with 5%PVP alcoholic solution system soft material, granulate with 20 mesh sieves, drying adds magnesium stearate, behind the mixing, on single punch tablet machine, dash the nail compressed tablet heart with 7 millimeters scrobiculas of φ.The sheet heart that makes is carried out film coating with 15% yellow Opadry coating solution, again in 40 ℃ dry 6 hours down, promptly get tablet.Survey dissolution: oar method, 75 rev/mins, 0.4% sodium lauryl sulphate 500ml is a dissolution medium, stripping in 40 minutes stripping 96.2% in 89.1%, 80 minute.
The thinking that we begin be according in, two dissolution determination requirements of state's pharmacopeia version in 2000, slightly solubility medicine dissolution in 40 minutes reaches more than 70%, prescription VII well meets the Chinese Pharmacopoeia requirement, but aranidipine belongs to slow-acting drug, and long-acting release more can reach one day a slice administering effect.Our bonded products character, The effect the stripping characteristics of external sample, and by two requirements of Chinese Pharmacopoeia version in 2000 about enteric coated preparation drug release determination method, according to appendix X D drug release determination method second method, dissolution method (appendix X C) first subtraction unit is measured external product, experimental result shows, external product is after the 0.1mol/L hydrochloric acid solution discharges two hours (acid resistance test), in the pH6.8 phosphate buffer, discharged 98% through 3 hours, basic release fully, and in the pH7.4 phosphate buffer, just discharged 97% in 1 hour, in conjunction with documents and materials and experimental result, we have screened this product prescription again, new recipe and external product release are compared, basically identical in the pH6.8 phosphate buffer, in the pH7.4 phosphate buffer, want slow 30 minutes, consider all complete substantially stripping in 3 hours in the pH6.8 phosphate buffer of external product and this product, we think that in the pH7.4 phosphate buffer difference of release does not influence the effectiveness of medicine, finally mainly per sample in the pH6.8 phosphate buffer release conditions selected new recipe, and new recipe has been made The effect.
External sample (granule) dissolution determination
| 3 minutes | 10 minutes | 20 minutes | 40 minutes | 80 minutes | |
| The 0.4%SDS aqueous solution | 4.4％ | 28％ | 32.9％ | 40％ | 45％ |
The external different dissolution medium dissolution determinations of sample (granule)
| Dissolution medium | Stripping quantity | |||
| 0.1mol/L | Stripping in 2 hours 0.77% 1.22% | |||
| 15 minutes | 25 minutes | 35 minutes | 45 minutes | |
| The PH6.8 buffer | 17.5％ | 30.96％ | 35.00％ | 44.31％ |
| The PH7.4 buffer | 38.28％ | 73.99％ | 103.78％ | 117.58％ |
We have selected for use lactose, starch, microcrystalline Cellulose as main filler in the prescription, replace hydroxypropyl methylcellulose with pH according to the robust material acrylic resin and make dispersant.Pass through experiment sieving, select for use the acrylic resin (Eudragit L100 and S100) of different model to make dispersant, made the granule of two kinds of different rate of releasing drug, by regulating two kinds of particulate different proportions, control the release in vitro behavior of product, discover, by two requirements of Chinese Pharmacopoeia version in 2000 about enteric coated preparation drug release determination method, according to appendix X D drug release determination method second method, dissolution method (appendix X C) first subtraction unit is measured, when identical coating is write out a prescription, when the ratio of granule A and granule B is 80: 20, prepared tablet and external product release in vitro behavior basically identical.The outer HPMC5cps that adds selects for use magnesium stearate as lubricant, institute's tablet agent hardness height, smooth surface as dry adhesives.Screening process sees following table for details.
Table 1 aranidipine enteric coatel tablets prescription screening table
Different prescriptions of Fig. 1 and external sample after acidproof 2 hours in the pH6.8 phosphate buffer full releasing curve diagram.By table 1 and Fig. 1 as can be seen, the release conditions of prescription 3 is the most approaching with external sample, and new recipe finally is chosen as prescription 3.
In existing report, acrylic resin just is used for enteric coatings as acid resisting material because have pH according to patience, we are used for the tablet label with relatively large acrylic resin (Eudragit L100 and S100) and hydroxypropyl emthylcellulose, be in order to reach the purpose of slow release, and must be consistent with external particle release degree, have only when the ratio of granule A and granule B is 80: 20 just to reach this requirement, reach the purpose that was administered once in a day.
Influence factor's investigation:
Make tablet by prescription 3, every contains principal agent 5mg, and compressibility is good.Flat appearance is smooth, and the hardness height meets the pharmacopeia requirement.
Behind the tablet coating of making, be exposed to high temperature (60 ℃), high humidity (RH92.5%, room temperature), (its stability under high temperature, high humidity, high light condition is studied in 4500 ± 500Lx) times acceleration 10 days to light.Parameter result of variations such as outward appearance, related substance, content see Table 2, and determination of related substances the results are shown in Figure 2a-5b.
Table 2 coated tablet accelerated stability under high temperature, super-humid conditions is investigated the result
| Acceleration environment | Observation index | ||||
| Outward appearance | Release (%) | Content (%) | Related substance (%) | ||
| Acidproof 2h | PH6.8 buffer 2 hours | ||||
| Before the acceleration | Smooth smooth | 0.6 | 86.7. | 99.1 | 0.24 |
| High temperature | Smooth smooth | 0.8 | 87.0 | 97.8 | 0.28 |
| High humidity | Smooth smooth | 0.8 | 81.4 | 99.5 | 0.32 |
| Light | Smooth smooth | 0.5 | 80.0 | 101.0 | 0.26 |
By result in the table as can be known, high temperature, high humidity, illumination do not have influence substantially to release, content, the related substance of aranidipine enteric coatel tablets, compare with the uncoated tablets photo damage, and the light stability of coated tablet obviously improves, the suggestion packing is answered shading, sealing, and the place preserves in the cool place.
The amplification preparation of sample and quality testing result:
By prescription 3, amplify three batches in sample (5000 every batch), lot number 04101001,04101102,04101203, article five, full release profiles average result compares with external sample, see Table 3, by table as seen, amplify sample acidproof (0.1mol/L hydrochloric acid solution) after two hours, release and external sample basically identical in the pH6.8 phosphate buffer.
Table 3 amplifies three batches of full release profiles averages and compares with external sample
| External sample (n=6) | 04101001 batch | 04101102 batch | 04101203 batch | |||
| Average 1 (n=6) | Average 2 (n=6) | Average 3 (n=6) | Average (n=6) | Average (n=6) | ||
| Acidproof 2 hours releases (%) | 0.8 | 0.78 | 0.84 | 0.61 | 0.59 | 1.67 |
| Time (minute) | PH6.8 phosphate buffer release (%) | |||||
| 30 | 22 | 12.3 | 12.1 | 9.9 | 13.6 | 13.8 |
| 60 | 53 | 51.5 | 49.3 | 46.3 | 41.5 | 42.8 |
| 90 | 70 | 72.0 | 70.2 | 67 | 67.2 | 66.7 |
| 120 | 82 | 84.7 | 86.4 | 80.6 | 82.6 | 86.9 |
| 150 | 88 | 89.4 | 95.4 | 90.5 | 91.3 | 93.9 |
| 180 | 98 | 94.0 | 98.4 | 96.7 | 97.3 | 99.5 |
| 210 | 99.5 | 99.3 | 98.7 | 99.3 | 99.9 | |
Fig. 2 amplifies three batches of full releasing curve diagram averages and external sample comparative graph.This product prescription sees Table 4 through content, release and related substance testing result, thinks the prescription composition rationally, feasible process, reliable in quality.
Table 4 amplifies three batch sample content, release, related substance testing result
| Lot number | Outward appearance | Content (%) | Release (%) | Related substance (%) | |
| Acidproof 2 hours | PH6.8 phosphate buffer (2 hours) | ||||
| 04101001 | This product is the casing sheet, removes behind the coating to yellow | 99.5 | 0.78 | 84.7 | 0.23 |
| 04101102 | This product is the casing sheet, removes behind the coating to yellow | 99.0 | 0.59 | 82.6 | 0.20 |
| 04101203 | This product is the casing sheet, removes behind the coating to yellow | 100.4 | 1.67 | 86.9 | 0.21 |
The invention effect: treatment hypertension enteric coatel tablets (trade name: the aranidipine enteric coatel tablets) have the bioavailability height, onset is slow, effect is lasting, every day is once oral, easy to use, improve patient's compliance greatly, aranidipine is that curative effect is the strongest in the present dihydropyridines medicine, effect is one of the most persistent antihypertensive drugs, can reduce broad masses of the people's financial burden to a great extent.
Description of drawings
Fig. 1 be different prescriptions and external sample after acidproof 2 hours in the pH6.8 phosphate buffer full releasing curve diagram.
Fig. 2 amplifies three batches of full releasing curve diagram averages and external sample comparative graph.
The specific embodiment
Embodiment: treatment hypertension enteric coatel tablets (trade name: the prescription aranidipine enteric coatel tablets):
1) label (1000):
Aranidipine 5g
Acrylic resin (Eudragit L100) 20g
Acrylic resin (Eudragit S100) 5g
Lactose 80g
Starch 80g
Microcrystalline Cellulose 10g
Hydroxypropyl emthylcellulose (HPMC5cps) 10g
Magnesium stearate 1g
Make 1000 211g
2) enteric coating liquid prescription:
Acrylic resin (L100) 10g
Polyethylene glycol 6000 1g
Pulvis Talci 2g
Titanium dioxide 2g
85% ethanol 200mL
Pigment is an amount of
Coating weightening finish 4～6%
3) preparation technology's (lucifuge operation):
A, tablet producing technology
A. adjuvant is crossed 100 mesh sieves.
B. aranidipine 5g, Eudragit E udragit L100 25g are dissolved in the 500ml80% alcoholic solution, are made into A solution.
C. aranidipine 5g, Eudragit E udragit S100 25g are dissolved in the 500ml80% alcoholic solution, are made into B solution.
D. take by weighing two parts of mixed accessories, every part contains lactose 80g, starch 80g, microcrystalline Cellulose 10g, crosses 40 mesh sieve mixings.
E. a copy of it mixed accessories being packed in the fluid bed, is binding agent with A solution, and marumerization is granulated, and obtains granule A.
F. another part mixed accessories being packed in the fluid bed, is binding agent with B solution, and marumerization is granulated, and obtains granule B.
G.24 the order granulate is pressed the label prescription, and (granule A: granule B=80: 20) mixing adds hydroxypropyl emthylcellulose and magnesium stearate, with the abundant mixing of hybrid particles in proportion with two kinds of granules.
H. use 9 millimeters scrobicula drifts of φ tabletting on single punch tablet machine.
B, tablet coating technology
Eudragit E udragit L100 powder is with an amount of 85% ethanol swelling, and placement is spent the night, ultrasonic abundant dissolving, add polyethylene glycol 6000, add 85% ethanol to full dose after stirring evenly dissolving, add Pulvis Talci, titanium dioxide and pigment and cross colloid mill 5～6 times, after 120 mesh sieves, standby.
Tablet coating is to 4～6%, 40 ℃ of dry 2h of label weightening finish.Taking-up room temperature packing.
Claims (2)
1, a kind of treatment hypertension drug, this effective elements of the medicine is an aranidipine, it is characterized in that preparing enteric coatel tablets with former, the adjuvant of following weight proportion:
A) label prepares with former, the adjuvant of following weight proportion:
Aranidipine 5g
Acrylic resin L100 20g
Acrylic resin S100 accompanies 5g
Lactose 80g
Starch 80g
Microcrystalline Cellulose 10g
Hydroxypropyl emthylcellulose 10g
Magnesium stearate 1g
Make 1000 211g
B) enteric coating liquid prepares with following materials of weight proportions:
Acrylic resin L100 10g
Polyethylene glycol 6000 1g
Pulvis Talci 2g
Titanium dioxide 2g
85% ethanol 200mL
Pigment is an amount of
Coating weightening finish 4～6%.
2, a kind of preparation method for the treatment of hypertension drug is characterized in that
A, label preparation method:
A. adjuvant is crossed 100 mesh sieves;
B. aranidipine 5g, Eudragit E udragit L100 25g are dissolved in 500ml 80% alcoholic solution, are made into A solution;
C. aranidipine 5g, Eudragit E udragit S100 25g are dissolved in 500ml 80% alcoholic solution, are made into B solution;
D. take by weighing two parts of mixed accessories, every part contains lactose 80g, starch 80g, microcrystalline Cellulose 10g, crosses 40 mesh sieve mixings;
E. a copy of it mixed accessories being packed in the fluid bed, is binding agent with A solution, and marumerization is granulated, and obtains granule A;
F. another part mixed accessories being packed in the fluid bed, is binding agent with B solution, and marumerization is granulated, and obtains granule B;
G.24 the order granulate is pressed the label prescription, and (granule A: granule B=80: 20) mixing adds hydroxypropyl emthylcellulose and magnesium stearate, with the abundant mixing of hybrid particles in proportion with two kinds of granules;
H. use 9 millimeters scrobicula drifts of φ tabletting on single punch tablet machine;
B, tablet coating technology:
Acrylic resin L100 powder is with an amount of 85% ethanol swelling, and placement is spent the night, ultrasonic abundant dissolving, add polyethylene glycol 6000, add 85% ethanol to full dose after stirring evenly dissolving, add Pulvis Talci, titanium dioxide and pigment and cross colloid mill 5～6 times, after 120 mesh sieves, standby;
Tablet coating takes out the room temperature packing to 4～6%, 40 ℃ of dry 2h of label weightening finish.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100156918A CN100413502C (en) | 2006-09-15 | 2006-09-15 | Hypertension treating medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100156918A CN100413502C (en) | 2006-09-15 | 2006-09-15 | Hypertension treating medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1931166A true CN1931166A (en) | 2007-03-21 |
| CN100413502C CN100413502C (en) | 2008-08-27 |
Family
ID=37877289
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006100156918A Active CN100413502C (en) | 2006-09-15 | 2006-09-15 | Hypertension treating medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100413502C (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104758265A (en) * | 2014-01-07 | 2015-07-08 | 四川海思科制药有限公司 | Ranolazine sustained release tablet medicine composition and preparation method thereof |
| CN114432254A (en) * | 2021-12-30 | 2022-05-06 | 南通联亚药业有限公司 | Nifedipine controlled release tablet |
| CN115645402A (en) * | 2022-11-22 | 2023-01-31 | 浙江工业大学 | Application of aranidipine in preparation of medicine for treating or preventing acute myocardial infarction |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1456148A (en) * | 2003-03-26 | 2003-11-19 | 北京东方凯恩医药科技有限公司 | Use of enlerogastric dynamic medicine in preparation of colonic orientation medicinal composition |
| CN100441193C (en) * | 2005-01-11 | 2008-12-10 | 石药集团欧意药业有限公司 | Antipyretic and analgetic aspirin enteric-coated preparation and production thereof |
-
2006
- 2006-09-15 CN CNB2006100156918A patent/CN100413502C/en active Active
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104758265A (en) * | 2014-01-07 | 2015-07-08 | 四川海思科制药有限公司 | Ranolazine sustained release tablet medicine composition and preparation method thereof |
| CN104758265B (en) * | 2014-01-07 | 2019-05-17 | 四川海思科制药有限公司 | A kind of ranolazine sustained release tablet medicament composition and preparation method thereof |
| CN114432254A (en) * | 2021-12-30 | 2022-05-06 | 南通联亚药业有限公司 | Nifedipine controlled release tablet |
| CN115645402A (en) * | 2022-11-22 | 2023-01-31 | 浙江工业大学 | Application of aranidipine in preparation of medicine for treating or preventing acute myocardial infarction |
Also Published As
| Publication number | Publication date |
|---|---|
| CN100413502C (en) | 2008-08-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1211086C (en) | Sustained release ranolazine formulations | |
| CN1029935C (en) | Pharmaceutical preparation and process for same | |
| CN1023293C (en) | Controlling-release preparation | |
| CN1883458A (en) | Enteric coated preparation of lansoprazole sodium and preparation method thereof | |
| CN1917862A (en) | Dosage form that is safeguarded from abuse | |
| CN1023191C (en) | Process for producing sustained release ibuprofen preparation | |
| CN1032402C (en) | Granulated medicinal composition and the prepn thereof | |
| CN1437483A (en) | Oral preparations for diabetes | |
| CN101073563A (en) | Chiral composition containing dextrothyroxine buprofenli and levomethadyl cysteliqin and its double slow-releasing tablet | |
| CN1729005A (en) | Pharmaceutical dosage forms of biguanide-sulfonylurea combinations | |
| CN1931166A (en) | Hypertension treating medicine | |
| CN101032462A (en) | Mexiletine Hydrochloride slow release reagent and preparing method thereof | |
| CN1443535A (en) | Tegasevod maleate oral preparation and its preparation process-for curing intestinal irritability syndrome | |
| CN101028518A (en) | Medicinal composition containing silver ester medicine and ibobulodine | |
| CN1853634A (en) | Composition comprising itraconazole for oral administration | |
| CN1265785C (en) | Chrono-slow-releasing prepn. hydrochloride verapamil | |
| CN1303990C (en) | Sodium ferulate oral disintegrating tablet and its preparation process | |
| CN1543943A (en) | Oral silybin sustained release agent and preparation thereof | |
| CN1835742A (en) | Preparing method for controlled released type tablet tamsulosin hcl and the tablet thereof | |
| CN1895250A (en) | Gliquilone slow-releasing preparation | |
| CN100336511C (en) | Release-controlled oral Roxithromycin formulation | |
| CN1297263C (en) | Calcium gluconate oral disintegrating tablet and its preparation process | |
| CN1298318C (en) | Sodium ferulic acid osmosis pump controlled release formulation and its preparation method | |
| CN1209109C (en) | Slow-releasing acipimox tablet | |
| CN1552327A (en) | Oral ofloxacin control-sustained releasing medicinal composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |