CN1868477A - Formula of Reynoldazine hydrochloride prepn. - Google Patents
Formula of Reynoldazine hydrochloride prepn. Download PDFInfo
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- CN1868477A CN1868477A CNA2006100867835A CN200610086783A CN1868477A CN 1868477 A CN1868477 A CN 1868477A CN A2006100867835 A CNA2006100867835 A CN A2006100867835A CN 200610086783 A CN200610086783 A CN 200610086783A CN 1868477 A CN1868477 A CN 1868477A
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- ranolazine hydrochloride
- hydrochloride
- oral formulations
- magnesium stearate
- ranolazine
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Abstract
A compound reynoldazine hydrochloride is prepared from the reynoldazine hydrochloride and the assistant chosen from diluent, adhesive and lubricant.
Description
Technical field:
The present invention relates to the anginal medicine novel formulation of a kind of treatment, particularly the new prescription and the preparation technology of ranolazine hydrochloride tablet.
Background technology:
Angina pectoris (Angina Pectoris) is that the oxygen delivery capacity by coronary flow can not satisfy cardiac muscle and the demand of oxygen caused the blood oxygen demand balance caused clinical syndrome of lacking of proper care, and is the modal clinical disease of coronary heart disease.Accumulating of the metabolite that the myocardial ischemia metabolism produces such as lactic acid, histamine and potassium ion etc., stimulate sympathetic nerve to import maincenter into, show as back paroxysmal colic or vexed pain in pareordia or the breastbone during outbreak, pain is radiation-curable to neck root, left shoulder, left upper arm, epigastrium or back.Weight does not wait, and is interrupted outbreak repeatedly, and the persistent period of at every turn showing effect is of short duration.
Under the normal condition, 60～70% the beta oxidations that cardiac energy (ATP) is supplied with from free fatty, 20～30% from glucose oxidase, and 5～10% from glycolysis.Myocardial ischemia can cause a series of Developmental and Metabolic Disorder usually, so improve myocardial metabolism, makes full use of limited oxygen and produces ATP more efficiently, but alleviate myocardial ischemia, thereby proposed by intervening the new ideas of energy metabolism of myocardial treatment ischemic heart desease.
Ranolazine hydrochloride is the angina pectoris metabolism medicine that has unique effect mechanism by Syntex (Roche) company, Kissei company and the joint research of CV Therapeutics company, chemical name is: 1-[3-(2-methoxyl group phenoxy group)-2-hydroxypropyl]-4-[(2, the 6-3,5-dimethylphenyl) amino carbonyl methyl] the piperazine hydrochloride semihydrate
Chemical structural formula is:
Molecular formula: C
24H
33N
3O
42HCl0.5H
2O
This product is a kind of partial fatty acid oxidation (pFOX) inhibitor.Ranolazine hydrochloride can be brought into play its antianginal effect under the condition that does not change hemodynamic parameter.These characteristics have obtained confirmation in II that CV Therapeutics company carries out, III clinical trial phase.Ranolazine hydrochloride has significant function of resisting myocardial ischemia, and its energy significant prolongation movement time reduces the angina pectoris attacks frequency.Ranolazine hydrochloride is oral significantly to reduce the rising amplitude of ST-T ripple due to the epinephrine, shows that ranolazine hydrochloride has stronger protective effect to cardiac muscle.Ranolazine hydrochloride is to heart failure and evident in efficacy with the chronic angina pectoris patient of congestive heart failure.
Ranolazine hydrochloride can suppress the beta-oxidation of fatty acid, and activates pyruvic dehydrogenase (PDH) and the increase glucose oxidase, reduces the content of S-acetyl-coenzyme-A in the cell.This metabolic conversion can increase the ATP that consumption the produced amount of unit mole oxygen, reduces the content of lactic acid, alleviates the acidosis degree, keeps the normal function of cardiac muscular tissue under the situation that myocardial oxygen delivery reduces.Studies show that ranolazine hydrochloride can suppress respiratory chain complex I near mitochondrial rotenone target site, and this inhibitory action is reversible; The affinity that its affinity to the mitochondrial membrane that breaks is compared coupling connection and decoupling zero on line plastochondria film (both are in the different-energy state) is strong, perhaps, this character of ranolazine hydrochloride can reduce the consumption of damaged tissue to oxygen, plays a part certain to improving myocardial ischemia.Ranolazine hydrochloride also has weak β
1, β
2The adrenergic aceptor antagonist activity; It has only faint influence to the tranquillization calcium current, but can weaken the calcium current that β-adrenergic receptor causes greatly.
The documents and materials of relevant ranolazine hydrochloride have: EP12644, EP483932, EP407780, WO9426266, WO0013686, WO0113907, WO0207716
Ranolazine hydrochloride is owing to the reason of molecular structure contains a certain amount of water of crystallization, the also easy simultaneously moisture absorption, therefore make the ordinary preparation instability, place certain hour in room temperature, it is bad stripping to occur, simultaneously because it draws moist, mobile relatively poor, operation easier is big when making preparation, makes that tablet needs coating, is loaded in the air-tight bottle, capsule reply capsule shells is carried out encapsulation process, and requires to keep away wet and oxygen, has influenced the medicine storage.The present invention has found the prescription and the preparation method that are fit to ranolazine hydrochloride is made tablet through screening, has solved the problems referred to above, therefore proposes the present invention.
Summary of the invention:
The invention provides a kind of prescription and preparation method of ranolazine hydrochloride tablet.
Ranolazine hydrochloride tablet of the present invention is made up of active constituents of medicine and pharmaceutic adjuvant, and wherein active constituents of medicine is a ranolazine hydrochloride, and pharmaceutic adjuvant is selected from diluent, binding agent, lubricant.
Wherein said diluent is selected from microcrystalline Cellulose, hydroxypropyl methylcellulose, lactose, starch, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose.Hydroxypropyl methylcellulose preferably, wherein hydroxypropyl methylcellulose hydroxypropyl methylcellulose E preferably
15
Described binding agent is selected from the alcoholic solution of hyprolose, polyvidone.Polyvidone preferably, wherein polyvidone 30 POVIDONE K 30 BP/USP preferably
30
Described lubricant is selected from magnesium stearate, Pulvis Talci, preferably magnesium stearate.
Tablet of the present invention, wherein to account for the percentage by weight of tablet total amount be 60-95% to the amount of ranolazine hydrochloride in tablet, all the other promptly contain the pharmaceutic adjuvant of 5-40% for pharmaceutic adjuvant.The present invention preferably fills a prescription as follows at the percentage by weight of tablet with each constituent of pharmaceutic adjuvant:
| Component | Weight range (wt%) | Preferred weight range (wt%) |
| Ranolazine hydrochloride | 60-95 | 70-95 |
| Diluent | 1-35 | 2-20 |
| Binding agent | 2-10 | 3-7 |
| Lubricant | 0.2-3 | 0.5-2 |
Be specifically as follows:
| Component | Weight range (wt%) | Preferred weight range (wt%) |
| Ranolazine hydrochloride | 60-95 | 70-95 |
| Hydroxypropyl methylcellulose E 15 | 1-35 | 2-20 |
| 30 POVIDONE K 30 BP/USP 30 | 2-10 | 3-7 |
| Magnesium stearate | 0.2-3 | 0.5-2 |
Prescription of the present invention obtains through screening,
Preferred prescription through the present invention's screening consists of:
Ranolazine hydrochloride 200-400g
Hydroxypropyl methylcellulose E
1515-30g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 62.5-300ml
Magnesium stearate 3-6g
Make 1000
Most preferred prescription consists of:
Ranolazine hydrochloride 200g (amounting to aqueous 203.6g)
Hydroxypropyl methylcellulose E
1515g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 100-150ml
Magnesium stearate 3g
Make 1000
It is as follows that most preferred prescription of the present invention is formed its screening process:
With reference to this product physicochemical property, dissolve in water according to this product, and absorption value is stable in 3h, is the dissolution determination medium with water, selects for use the pharmaceutic adjuvant of stable performance commonly used to carry out prescription screening.
The dissolution test data can instruct and work out best prescription and technology in prescription screening, to reach the biological effectiveness of expection, but there is no absolute dependency relation between the stripping of effective ingredient and the bioavailability of medicament, only when the dissolution rate of medicine is equal to or less than medicine absorption in vivo speed, dissolution rate becomes rate-limiting factor, just certain dependency can be arranged between the two, therefore must filter out comparatively ideal stripping curve, general common gastric soluble tablet requires to have disintegrative preferably, stripping property, stripping curve is steady rising, so that medicine can effectively absorb, guarantees curative effect, and be sampling time point with this stripping curve flex point, formulate the stripping of this product and limit the quantity of, according to the requirement of two appendix XC of Chinese Pharmacopoeia version in 2005 dissolution method, stripping in 45 minutes is not less than and indicates 70% of content.This product was carried out according to requiring in when prescription screening.And require in the preparation process, the compressibility of tablet will be got well, the slice, thin piece any surface finish that is pressed into, and color and luster is even, and has certain degree of hardness, is convenient to coating, transportation.And meet the requirement of health examination.
This product through repetition test repeatedly, by adjusting prescription proportioning and consumption, is improved perfect for the variety of problems that occurs when prescription screening.When the screening prescription, should make this product that stripping curve is preferably arranged, reduce of the influence of used adjuvant again as far as possible this product total impurities.
Different prescription screening situations are as follows:
Write out a prescription one every
Ranolazine hydrochloride 200mg
Hydroxypropyl methylcellulose E
540mg
Microcrystalline Cellulose MCC102 17mg
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution is an amount of
Magnesium stearate 3mg
Situation: this prescription is diluent with the hydroxypropyl methylcellulose, is dry adhesive and short disintegrating agent with microcrystalline Cellulose MCC, with 8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution is a binding agent system soft material, crosses 20 mesh sieve system wet granulars, and oven dry back mobility of particle is better, makes the slice, thin piece any surface finish, and this product is a gastric soluble tablet, with reference to 2005 editions two appendix dissolution methods of Chinese Pharmacopoeia, measures its dissolution.
Test parameters:
Dissolving-out method: change the basket method
Solvent: water 900ml
Rotating speed: 100 rev/mins
Temperature: 37 ± 0.5 ℃
Detection method: ultraviolet spectrophotometry
Detect wavelength: 271nm
Measurement result sees Table 1.
Table 1 prescription one dissolution determination result (n=6)
| Time (branch) | 10 | 20 | 30 | 45 |
| Stripping quantity (%) | 50.28 | 80.76 | 98.27 | 97.27 |
Measurement result: the tablet stripping of this prescription is very fast, and dissolution rate had reached 50% in 10 minutes.Stripping is too fast, and dissolution rate does not become rate-limiting factor, must further adjust.
Write out a prescription two every
Ranolazine hydrochloride 200mg
Hydroxypropyl methylcellulose E
560mg
Microcrystalline Cellulose MCC102 17mg
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution is an amount of
Magnesium stearate 3mg
Situation: this product on prescription one basis, increased certain viscosity is arranged hydroxypropyl methylcellulose to keep certain dissolution rate.Dissolution determination the results are shown in Table 2.
Table 2 prescription two dissolution determination results (n=6)
| Time (branch) | 10 | 20 | 30 | 45 | 60 |
| Stripping quantity | 35.24 | 61.19 | 79.11 | 91.54 | 90.49 |
Measurement result: the stripping curve of this prescription is steady rising: the stripping curve flex point is about 45 minutes, and stripping curve is comparatively reasonable, but adjuvant has certain influence to principal agent total impurities mensuration.
Write out a prescription three every
Ranolazine hydrochloride 200mg
Hydroxypropyl methylcellulose E
1560mg
Microcrystalline Cellulose MCC102 17mg
8% 30 POVIDONE K 30 BP/USP
30Aqueous solution is an amount of
Magnesium stearate 3mg
Situation: this product adopts hydroxypropyl methylcellulose E
15Be diluent, examination is with 8% 30 POVIDONE K 30 BP/USP
30Aqueous solution is a binding agent, but finds that this product principal agent is very easily soluble in water in system during soft material, therefore adds behind the binding agent principal agent and absorbs water thinningly immediately, finally becomes solution, can't granulate, and shows that this product should not be the binding agent of solvent in order to water.
Write out a prescription four every
Ranolazine hydrochloride 200mg
Hydroxypropyl methylcellulose E
1515mg
Microcrystalline Cellulose MCC102 30mg
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution is an amount of
Magnesium stearate 3mg
Situation: this product adopts hydroxypropyl methylcellulose E
15, its viscosity is higher than hydroxypropyl methylcellulose E
5, can reduce supplementary product consumption thus, and keep similar dissolution rate, dissolution determination the results are shown in Table 3.
Table 3 prescription four dissolution determination results
| Time (branch) | 10 | 20 | 30 | 45 |
| Dissolution (%) | 48.68 | 82.36 | 94.29 | 94.65 |
Measurement result: this prescription is with hydroxypropyl methylcellulose E
15Be diluent, supplementary product consumption reduces relatively, but the stripping curve rising is very fast, still must adjust.
Write out a prescription five every
Ranolazine hydrochloride 200mg
Hydroxypropyl methylcellulose E
1515mg
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution is an amount of
Magnesium stearate 3mg
Situation: on the basis of prescription four,, adjust the kind and the consumption of adjuvant, to reduce the influence that adjuvant is measured the principal agent total impurities through repetition test.Change the dissolution determination condition simultaneously, promptly with 100 rev/mins and 50 rev/mins five the tablet of writing out a prescription is carried out dissolution determination respectively.
The tablet compressibility of this prescription is good, and the slice, thin piece that is pressed into has certain degree of hardness, any surface finish, and color and luster is even, is suitable for coating.
The dissolution determination situation sees Table 4.
Table 4 prescription five dissolution determination results
| Time (branch) | 10 | 20 | 30 | 45 | 60 |
| Dissolution (%) during 100 rev/mins of dissolutions in the time of 50 rev/mins (%) | 38.16 53.61 | 67.63 87.43 | 86.97 100.56 | 100.03 100.01 | 100.01 100.21 |
Measurement result shows: this prescription tablet dissolution rate in the time of 50 rev/mins is steady rising, and the stripping curve flex point is about 45 minutes, and stripping curve is comparatively desirable.
For the present invention, can be prepared into according to the routine techniques of galenic pharmacy tablet of the present invention as:
The preparation of tablet can be put ranolazine hydrochloride and diluent in the three-dimensional mixer; mix homogeneously; add suitable amount of adhesive and make soft material; soft material is made wet granular through suitable screen cloth; granulate sieves after the drying; add the dried granule mix homogeneously of selectable lubricant and gained, tabletting promptly can be made Film coated tablets as required.Coating adopts the galenic pharmacy routine techniques to get final product.
In addition, the present invention also can become any oral dosage form that is fit to according to formulation of the present invention as required, as capsule, and granule, slow releasing tablet, slow releasing capsule etc.
Other oral formulations can prepare as follows:
Hard capsule: with ranolazine hydrochloride and the even dry mixture that gets of selectable mixed with excipients, the employing wet granulation process is granulated, with wet grain drying, the granulate that sieves, with selectable lubricant (as magnesium stearate) and other fluidizer mix homogeneously, in the hard capsule of packing into.
Granule: ranolazine hydrochloride and selectable mixed with excipients is even, adopt wet granulation process to granulate, with wet grain drying, the granulate that sieves, classification, coating flavoring, packing.
Slow releasing tablet: ranolazine hydrochloride and selectable diluent are put in the three-dimensional mixer, mix homogeneously, pack into piller with The suitable solvent (as Aquacoat), also available in case of necessity The suitable solvent or mixture process, tabletting promptly gets label, utilizes retardance material bag film-coat at last.
Slow releasing capsule: ranolazine hydrochloride and selectable diluent are put in the three-dimensional mixer, and mix homogeneously packs into piller with The suitable solvent (as Aquacoat), utilizes retardance material bag film-coat.With selectable lubricant (as magnesium stearate) and other fluidizer mix homogeneously, in the hard capsule of packing into.
Following stability experiment data and effect experimental data are used to illustrate beneficial effect of the present invention: the stability test data:
Abide by new drug evaluation relevant requirements, and with reference to the experimental technique of influence factor in the medicine guideline, the tablet of prescription five is carried out film coating.And the slice, thin piece behind the coating has been carried out the stability influence factor investigated.(placed 10 days under high temperature (60 ℃) of 4500Lx ± 500Lx) and high humidity (RH90% ± 5%) condition, data see Table 5 in illumination respectively.
The existing ranolazine hydrochloride coated tablet influence factor test (ten days) of table 5 with prescription
Result of the test shows: this product is through high temperature (60 ℃), high humidity (RH90% ± 5%) illumination (4500Lx) test ten days, appearance luster does not have significant change, under the super-humid conditions, the sheet sub-surface is sticking slightly, all the other no significant changes, content with 45 minutes in dissolution also consistent substantially with 0 day, total impurities does not also have significant change, and the total impurities of three kinds of influence factor's conditions after following 10 days is all less than 1%.
The specific embodiment:
Further specify the present invention by the following examples, but not as the restriction to this patent.
Embodiment 1
Ranolazine hydrochloride 200g (amounting to aqueous 203.6g)
Hydroxypropyl methylcellulose E
1515g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 150ml
Magnesium stearate 3g
Make 1000
Ranolazine hydrochloride is pulverized, crossed 80 mesh sieves, get recipe quantity ranolazine hydrochloride and recipe quantity hydroxypropyl methylcellulose E
15Mix homogeneously, add 8% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, (the gained granule is held dried granule with hand-tight, and hands loosens and causes granule and should not bond agglomerating for 60 ℃ of dryings, palm does not have that fine powder adheres to yet or should pulverize immediately when being twined with forefinger and thumb granule, the free from dampness sense) granulate adds magnesium stearate, mixing, tabletting, the bag film-coat.
Embodiment 2
Ranolazine hydrochloride 400g (amounting to aqueous 407.2g)
Hydroxypropyl methylcellulose E
1530g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 300ml
Magnesium stearate 6g
Make 1000
Ranolazine hydrochloride is pulverized, crossed 80 mesh sieves, get recipe quantity ranolazine hydrochloride and recipe quantity hydroxypropyl methylcellulose E
15Mix homogeneously, add 8% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, (the gained granule is held dried granule with hand-tight, and hands loosens and causes granule and should not bond agglomerating for 60 ℃ of dryings, palm does not have that fine powder adheres to yet or should pulverize immediately when being twined with forefinger and thumb granule, the free from dampness sense) granulate adds magnesium stearate, mixing, tabletting, the bag film-coat.
Embodiment 3
Ranolazine hydrochloride 200g (amounting to aqueous 203.6g)
Hydroxypropyl methylcellulose E
1545g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 80ml
Magnesium stearate 3g
Make 1000
Ranolazine hydrochloride is pulverized, crossed 80 mesh sieves, get recipe quantity ranolazine hydrochloride and recipe quantity hydroxypropyl methylcellulose E
15Mix homogeneously, add 8% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, (the gained granule is held dried granule with hand-tight, and hands loosens and causes granule and should not bond agglomerating for 60 ℃ of dryings, palm does not have that fine powder adheres to yet or should pulverize immediately when being twined with forefinger and thumb granule, the free from dampness sense) granulate adds magnesium stearate, mixing, tabletting, the bag film-coat.
Embodiment 4
Ranolazine hydrochloride 200g (amounting to aqueous 203.6g)
Hydroxypropyl methylcellulose E
155g
8% 30 POVIDONE K 30 BP/USP
30Alcoholic solution 62.5ml
Magnesium stearate 3g
Make 1000
Ranolazine hydrochloride is pulverized, crossed 80 mesh sieves, get recipe quantity ranolazine hydrochloride and recipe quantity hydroxypropyl methylcellulose E
15Mix homogeneously, add 8% polyvidone alcoholic solution system soft material, cross 18 mesh sieve system granules, (the gained granule is held dried granule with hand-tight, and hands loosens and causes granule and should not bond agglomerating for 60 ℃ of dryings, palm does not have that fine powder adheres to yet or should pulverize immediately when being twined with forefinger and thumb granule, the free from dampness sense) granulate adds magnesium stearate, mixing, tabletting, the bag film-coat.
Claims (10)
1. the oral formulations of a hydrochloric ranolazine is characterized in that: said preparation contains ranolazine hydrochloride and one or more pharmaceutically acceptable auxiliaries, and described adjuvant is selected from diluent, binding agent, lubricant; Described diluent is selected from microcrystalline Cellulose, hydroxypropyl methylcellulose, lactose, starch, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, polyvinylpolypyrrolidone, low-substituted hydroxypropyl cellulose, described binding agent is selected from the alcoholic solution of hyprolose, polyvidone, and described lubricant is selected from magnesium stearate, Pulvis Talci.
2. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Component Weight range (wt%)
Ranolazine hydrochloride 60-95
Diluent 1-35
Binding agent 2-10
Lubricant 0.2-3
3. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Component Weight range (wt%)
Ranolazine hydrochloride 70-95
Diluent 2-20
Binding agent 3-7
Lubricant 0.5-2
4. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Component Weight range (wt%)
Ranolazine hydrochloride 60-95
Hydroxypropyl methylcellulose E
15 1-35
30 POVIDONE K 30 BP/USP
30 2-10
Magnesium stearate 0.2-3
5. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Component Weight range (wt%)
Ranolazine hydrochloride 70-95
6. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Ranolazine hydrochloride 200-400g
Hydroxypropyl methylcellulose E
15 15-30g
8% 30 POVIDONE K 30 BP/USP
30Ethanol liquid
62.5-300ml
Magnesium stearate 3-6g
Make 1000
7. oral formulations as claimed in claim 1 is characterized in that, the proportioning of each component is as follows:
Ranolazine hydrochloride 200g (amounting to aqueous 203.6g)
Hydroxypropyl methylcellulose E
15 15g
8% 30 POVIDONE K 30 BP/USP
30Ethanol liquid
62.5-150ml
Magnesium stearate 3g
Make 1000
8. oral formulations as claimed in claim 1 is characterized in that said preparation unit contains the ranolazine hydrochloride of 200-400mg, is suitable for the patient and takes 3-4 time every day, each 3-4 preparation unit.
9, oral formulations as claimed in claim 1 is characterized in that said preparation is a tablet.
10, the preparation method of the oral formulations of claim 1 is characterized in that: through following steps,
1) compressed tablet: ranolazine hydrochloride and selectable diluent are put in the three-dimensional mixer, mix homogeneously, add suitable amount of adhesive and make soft material, soft material is made wet granular through suitable screen cloth, granulate sieves after the drying, add the dried granule mix homogeneously of selectable lubricant and gained, tabletting promptly gets label, wraps film-coat at last;
2) hard capsule: with ranolazine hydrochloride and the even dry mixture that gets of selectable mixed with excipients, the employing wet granulation process is granulated, with wet grain drying, the granulate that sieves, with selectable lubricant (as magnesium stearate) and other fluidizer mix homogeneously, in the hard capsule of packing into;
3) granule: ranolazine hydrochloride and selectable mixed with excipients is even, adopt wet granulation process to granulate, with wet grain drying, the granulate that sieves, classification, coating flavoring, packing;
4) slow releasing tablet: ranolazine hydrochloride and selectable diluent are put in the three-dimensional mixer, mix homogeneously, pack into piller with The suitable solvent (as Aquacoat), also available in case of necessity The suitable solvent or mixture process, tabletting promptly gets label, utilizes retardance material bag film-coat at last;
5) slow releasing capsule: ranolazine hydrochloride and selectable diluent are put in the three-dimensional mixer, and mix homogeneously packs into piller with The suitable solvent (as Aquacoat), utilizes retardance material bag film-coat.With selectable lubricant (as magnesium stearate) and other fluidizer mix homogeneously, in the hard capsule of packing into.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100867835A CN100455288C (en) | 2006-06-26 | 2006-06-26 | Formula of Reynoldazine hydrochloride prepn. |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006100867835A CN100455288C (en) | 2006-06-26 | 2006-06-26 | Formula of Reynoldazine hydrochloride prepn. |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1868477A true CN1868477A (en) | 2006-11-29 |
| CN100455288C CN100455288C (en) | 2009-01-28 |
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|---|---|---|---|
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110882316A (en) * | 2019-12-23 | 2020-03-17 | 卓和药业集团有限公司 | Compound preparation of anti-angina pectoris medicine and preparation method thereof |
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| CN110898024A (en) * | 2019-12-17 | 2020-03-24 | 卓和药业集团有限公司 | Pharmaceutical composition for treating angina pectoris and preparation method thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| US6479496B1 (en) * | 1998-09-10 | 2002-11-12 | Cv Therapeutics, Inc. | Methods for treating angina with ranolazine |
| CN1248690C (en) * | 2004-03-25 | 2006-04-05 | 华中师范大学 | Oral preparation containing ranolazine hydrochloride for treating cardiovascular disease |
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Cited By (1)
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| CN110882316A (en) * | 2019-12-23 | 2020-03-17 | 卓和药业集团有限公司 | Compound preparation of anti-angina pectoris medicine and preparation method thereof |
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