CN110898024A - Pharmaceutical composition for treating angina pectoris and preparation method thereof - Google Patents
Pharmaceutical composition for treating angina pectoris and preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4866—Organic macromolecular compounds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Abstract
The invention discloses a pharmaceutical composition for treating angina pectoris, which comprises a main drug and borneol, wherein the main drug is selected from ranolazine, ranolazine hydrochloride or pharmaceutically acceptable salts of ranolazine. The pharmaceutical composition for treating angina disclosed by the invention has a remarkable clinical curative effect especially on unstable angina and stable angina, and can reduce the administration dosage and improve the drug potency, so that the side effect of the drug is greatly reduced.
Description
FIELD
The invention relates to the technical field of pharmaceutical preparations, in particular to a pharmaceutical composition for treating angina and a preparation method thereof.
Background
Angina pectoris (anginapectoris) is a clinical syndrome caused by an acute, transient imbalance of oxygen supply and oxygen demand by the heart muscle. The clinical characteristic is paroxysmal chest squeezing pain sensation, which is mainly located at the back of the sternum, can be radiated to the precordial region, the left upper limb, the neck, the left shoulder and the back, usually occurs when fatigue or emotion is excited, the duration is a few minutes, the disease is most common in men after rest or nitrate preparation is used, and most patients are over 40 years old, and fatigue, emotion excitation, satiety, cold, rainy weather, acute circulatory failure and the like are common causes. Typical angina pectoris is often frequent in the morning under similar conditions; the pain usually gradually relieves after lasting for 3-5 minutes, and can be attacked once a day or a week or more times a day.
Angina pectoris is clinically classified into three clinical types of stable angina pectoris, unstable angina pectoris and variant angina pectoris. Stable angina pectoris (stable angina pectoris) is the most common type of angina pectoris in the clinic. It means that the disease condition is relatively stable within a long period of time (more than 1 month), and the frequency, the duration, the cause and the relieving mode of angina pectoris are all quite fixed. Its stability comprises two implications: one means stable disease condition; the other is that the coronary atherosclerotic plaque is stable and has no unstable factors such as ulcer, rupture, interlayer, thrombosis and the like. The pathological basis for stable angina is fixed stenosis from coronary atherosclerotic plaques.
Unstable angina pectoris (unstable angina pectoris), an acute cardiac event of coronary heart disease, is an important component of acute coronary syndrome, and is an intermediate clinical syndrome between chronic stable angina pectoris and acute myocardial infarction. The basic pathophysiological characteristic is that the coronary atherosclerotic plaque is unstable. The unstable angina pectoris has a multiterminal state change and can be converted into stable angina pectoris, and acute myocardial infarction and sudden death can be rapidly progressed, so that the correct recognition and treatment of the unstable angina pectoris have important clinical significance.
Variant angina is one of the spontaneous angina pectoris. Ischemic angina caused by coronary artery spasm was named "variant angina" in 1959, indicating that the onset of this angina was independent of activity. The pain usually occurs at rest and in daily activities, is heavier than common angina pectoris and lasts for several tens of seconds to 30 min; some of the attacks show a series of short-term attacks, each lasting for 1-2 min, appearing after a few minutes, are periodic, often occur at a certain time every day, especially in the middle of the night or in the early morning, the blood pressure of a patient is increased when the attack occurs, the blood pressure is reduced when the attack occurs for a few times, is irrelevant to fatigue and mental stress, has no obvious inducement, and is not relieved by lying in bed.
The existing anti-angina pectoris medicines mainly comprise 1. nitrate esters, wherein ① reduces myocardial oxygen consumption, and small dose of nitroglycerin can obviously expand venous blood vessels, reduce return blood volume, reduce intraventricular pressure, reduce ventricular wall tension, shorten ejection time, reduce myocardial oxygen consumption, slightly larger dose can obviously relax arterial blood vessels, reduce cardiac ejection resistance, thereby reducing left ventricular pressure and ventricular wall tension, reducing myocardial oxygen consumption, ② expands coronary artery to increase blood perfusion in an ischemic area, ③ reduces left ventricular filling pressure, increases endocardial blood supply, improves left ventricular compliance, ④ protects ischemic myocardial cells and relieves ischemic injury.
①, β receptor antagonist, the function of this kind of medicine is that the oxygen consumption of myocardium is reduced by β receptor antagonist, the myocardial contractility is weakened, the myocardial fiber shortening speed is slowed down, the heart rate is slowed down and the blood pressure is lowered by antagonizing β receptor, the oxygen consumption of myocardium can be reduced obviously, but it can inhibit the myocardial contractility and increase the ventricular volume, prolong the ventricular ejection time, and lead to the increase of myocardial oxygen consumption, but the total effect is still to reduce the myocardial oxygen consumption, ②, after the myocardial ischemia area blood supply coronary blood vessel β receptor is blocked, the difference of blood vessel tension between non-ischemia area and ischemia area is increased to promote the blood flow to the ischemia area which has been compensated and expanded, thus increase the blood flow of ischemia area.
3.① calcium channel blocker can weaken myocardial contractility, slow heart rate, relax blood vessel smooth muscle, reduce blood pressure, reduce heart load and reduce myocardial oxygen consumption, ② coronary blood vessel dilator has dilation action on larger transport blood vessel and small resistance blood vessel in coronary artery, especially has obvious action of relieving spasm of blood vessel in spastic state to increase blood perfusion in ischemic region, and can also increase collateral circulation and improve blood supply and oxygen supply in ischemic region ③ Ca2+ channel blocker for protecting myocardial cell by inhibiting external calcium inflow and reducing Ca2+ overload of ischemic myocardial cell to protect myocardial cell, for acute myocardial infarction, can narrow infarction range ④ inhibits platelet aggregation type angina, is related to platelet adhesion and aggregation, coronary artery blood flow reduction, most acute myocardial infarction is also caused by atherosclerotic plaque rupture, local formation of sudden occlusion of coronary artery, inner flow of calcium channel blocker is used for inhibiting Ca2+ 2 concentration of platelet aggregation, and inhibiting platelet aggregation.
In addition, ranolazine is the first choice of drugs for treating angina at present, has a unique action mechanism, has the effects of resisting myocardial ischemia, arrhythmia and heart failure, is approved by FDA in 2006-1 month, and is a ranolazine sustained-release film coated tablet with specifications of 500mg and 1000 mg. Ranolazine is a piperazine derivative that acts by partially inhibiting fatty acid metabolism, i.e., reducing fatty acid oxidation, and inducing glucose metabolism, and because glucose metabolism is more effective than fatty acid metabolism, it enables the heart to utilize oxygen more efficiently, because the regulatory mechanism of cardiac metabolism tends to convert energy metabolism substrates into glucose during myocardial ischemia, thereby increasing the efficiency of oxygen utilization. Glucose is now used as a substrate for energy metabolism and its utilization is increased because to produce the same energy, fatty acid oxidation requires more oxygen than glucose metabolism. Clinical tests and animal experiments show that the medicine can obviously improve the symptoms of angina patients and improve the exercise tolerance of the patients, and animals also find that the medicine can fully increase the cardiac ejection fraction and the myocardial oxygen consumption is reduced along with the increase of the ejection fraction. In view of the novel mechanism of action described above, oral ranolazine does not cause a slowing in heart rate and a drop in blood pressure. Can also prevent lactic acidosis and greatly enhance the use safety.
Currently, ranolazine generally exhibits vertigo (6.2%), headache (5.5%), constipation (4.5%) and nausea (4.4%). However, current data show that ranolazine carries a risk of QT-interval prolongation, which is likely to be the leading cause of cardiovascular death in this drug, and current clinical data show that ranolazine cardiovascular death events are not reduced compared to other therapeutic drugs and must be noted clinically.
In addition, the medicine can promote intestinal tumor increase of animal model, and improve abnormity and invasiveness of intestinal cells of mouse (spontaneous intestinal tumor model). Because the potency of the medicine is low, 500mg or 1000mg is needed to be taken every time, which is also the pharmacological basis for the occurrence of adverse reactions.
SUMMARY
In one aspect, the disclosure relates to a pharmaceutical composition for treating angina pectoris, which comprises a main drug and borneol, wherein the main drug is selected from ranolazine, ranolazine hydrochloride or a pharmaceutically acceptable salt of ranolazine.
In another aspect, the present disclosure relates to a method of preparing a pharmaceutical composition comprising the steps of:
mixing a main drug, microcrystalline cellulose and an ethyl methacrylate copolymer to obtain a mixture;
dissolving the mixture in an alkali solution to obtain sustained-release granules; and
mixing borneol, talcum powder and magnesium stearate with the sustained-release granules to obtain the pharmaceutical composition.
Detailed description of the invention
In the following description, certain specific details are included to provide a thorough understanding of various disclosed embodiments. One skilled in the relevant art will recognize, however, that the embodiments can be practiced without one or more of the specific details, or with other methods, components, materials, and so forth. Unless otherwise required by the disclosure, throughout the specification and the appended claims, the words "comprise", "comprising", and "have" are to be construed in an open, inclusive sense, i.e., "including but not limited to".
Reference throughout the specification to "one embodiment," "an embodiment," "in another embodiment," or "in certain embodiments" means that a particular reference element, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Thus, the appearances of the phrases "in one embodiment" or "in an embodiment" or "in another embodiment" or "in certain embodiments" in various places throughout this specification are not necessarily all referring to the same embodiment, and furthermore, particular elements, structures, or features may be combined in any suitable manner in one or more embodiments.
Definition of
In the present disclosure, the term "granulation" refers to a process of improving the flowability of a powder such that finer particles agglomerate into coarse powder aggregates. Granulation is the operation of processing the materials in the state of powder, melt, aqueous solution, etc. into granules with certain shape and size.
In the present disclosure, the term "borneol" refers to borneol, mandarin orange, borneol, tomatillo, borneol, plum ice, etc., which is a crystal extracted from the resin and volatile oil processed product of borneol of the family of campholaceae, and is almost pure dextroborneol. It is also synthesized by chemical method.
In the present disclosure, the term "talc" refers to a magnesium silicate mineral talc group talc, the main component of which is hydrous magnesium silicate, and the talc is obtained by crushing, treating with hydrochloric acid, washing with water, and drying.
In the present disclosure, the term "microcrystalline cellulose" refers to a purified, partially depolymerized cellulose, white, odorless, tasteless, crystalline powder composed of porous microparticles, primarily used as a filler.
In the present disclosure, the term "ethyl methacrylate copolymer" refers to a novel acrylic resin, which has the advantages of stable physical and chemical properties, no toxicity, no irritation, etc., and is mainly used as a coating material for sustained and controlled release preparations, and related substances are mainly monomer components of methacrylic acid and ethyl acrylate.
In the present disclosure, the term "hydroxypropylmethylcellulose" has thermal gelling properties, aqueous solution has surface activity, high transparency, stable performance, and is mainly used as an adhesive.
In the present disclosure, the term "magnesium stearate" refers to a white, light, non-gritty fine powder, which is used primarily as a lubricant, with appropriate amounts of lubricant providing anti-sticking, flow-enhancing, and lubricating properties, but excess lubricant can soften the tablet, resulting in a decrease in tablet hardness, an increase in friability, and the hydrophobic magnesium stearate can also result in a delay in disintegration and a decrease in dissolution of the tablet.
In the present disclosure, the term "opadry" refers to a film coating material used to meet the coating needs of different tablet types.
In the present disclosure, the term "purified water" refers to water for medical use prepared by distilling drinking water, ion exchange, reverse osmosis or other suitable method, without any additives.
In the present disclosure, the term "mesh" refers to the unit of measure, and the unit of measure mesh size refers to the size of the particles of the feedstock, generally expressed as the maximum length of the particles. The mesh is the size representing the mesh size of a standard screen. In the taylor standard sieve, the so-called mesh is the number of sieve openings in a 1 inch length and is simply called mesh.
Detailed Description
In one aspect, the disclosure relates to a pharmaceutical composition for treating angina pectoris, which comprises a main drug and borneol, wherein the main drug is selected from ranolazine, ranolazine hydrochloride or a pharmaceutically acceptable salt of ranolazine.
In certain embodiments, the weight ratio of the primary drug to borneol is from 1:1 to 10: 1.
In certain embodiments, the weight ratio of the primary drug to borneol is from 5:1 to 8: 1.
In certain embodiments, illustrative examples of pharmaceutically acceptable salts of ranolazine that can be used in the present disclosure include, but are not limited to, hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate and glutamate salts of ranolazine.
In certain embodiments, non-functional excipients are also included.
In certain embodiments, illustrative examples of non-functional excipients that can be used in the present disclosure include, but are not limited to, microcrystalline cellulose, ethyl methacrylate copolymer, hydroxypropyl methylcellulose, talc, magnesium stearate, and opadry.
In certain embodiments, the pharmaceutical composition is a tablet or capsule.
In certain embodiments, the tablet is a sustained release tablet.
In certain embodiments, the capsule is a sustained release capsule.
In another aspect, the present disclosure relates to a method of preparing a pharmaceutical composition comprising the steps of:
mixing a main drug, microcrystalline cellulose and an ethyl methacrylate copolymer to obtain a mixture;
dissolving the mixture in an alkali solution to obtain sustained-release granules; and
mixing borneol, talcum powder and magnesium stearate with the sustained-release granules to obtain the pharmaceutical composition.
In certain embodiments, illustrative examples of cardinal agents that can be used in the present disclosure include, but are not limited to, ranolazine hydrochloride, and pharmaceutically acceptable salts of ranolazine.
In certain embodiments, the weight ratio of the primary drug to borneol is from 1:1 to 10: 1.
In certain embodiments, the weight ratio of the primary drug to borneol is from 5:1 to 8: 1.
In certain embodiments, illustrative examples of pharmaceutically acceptable salts of ranolazine that can be used in the present disclosure include, but are not limited to, hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate and glutamate salts of ranolazine.
In certain embodiments, illustrative examples of alkali solutions that can be used in the present disclosure include, but are not limited to, sodium hydroxide solution, potassium carbonate solution, sodium carbonate solution, potassium hydrogen carbonate solution, sodium methoxide solution, and sodium ethoxide solution.
In certain embodiments, prior to pelletizing, further comprising mixing the mixture through a high speed pelletizer.
In certain embodiments, the mixing time is about 5 to 8 min.
In some embodiments, the step of stirring is further included after the slow release portion is dissolved in the alkaline solution.
In certain embodiments, the stirring time is about 3 to 5 min.
In certain embodiments, a drying step is included after granulation.
In certain embodiments, the drying temperature is about 30 ℃ to 100 ℃.
In certain embodiments, the drying temperature is about 0 ℃ to 80 ℃.
In certain embodiments, the drying temperature is about 60 ℃.
In certain embodiments, the drying time is from about 30 to 50 minutes, or the pellet moisture is controlled to be 3.0% or less.
In certain embodiments, greater than 70% of the sustained release particles in the sustained release granules have a particle size of about 20 mesh to 80 mesh.
In certain embodiments, the pharmaceutical composition is a tablet or capsule.
In certain embodiments, the pharmaceutical composition is a sustained release tablet.
In certain embodiments, the pharmaceutical composition is a sustained release capsule.
In certain embodiments, the tablets are coated.
In certain embodiments, the coating is performed using opadry.
Example 1
The embodiment discloses a pharmaceutical composition for treating angina pectoris, the dosage form of the pharmaceutical composition is a sustained-release tablet, and the pharmaceutical composition comprises the following components:
| composition (I) | Dosage/tablet |
| Ranolazine | 300mg |
| Borneol (borneol) | 60mg |
| Microcrystalline cellulose | 42mg |
| Ethyl methacrylate copolymer | 40mg |
| Hydroxypropyl methylcellulose | 8mg |
| Sodium hydroxide | 1.5mg |
| Magnesium stearate | 8.5mg |
| Talcum powder | 60mg |
| Opadry | 35mg |
| Purified water | 0.15mg |
The preparation process comprises the following steps:
1. the ranolazine, microcrystalline cellulose and ethyl methacrylate copolymer in the formula are uniformly mixed by a high-speed granulator.
2. Dissolving sodium hydroxide in purified water, adding into the above uniformly mixed materials, stirring, and granulating.
3. Drying at 60 deg.C to obtain sustained release granule.
4. Grinding Borneolum Syntheticum and pulvis Talci, adding into the above delayed release granule, mixing with three-dimensional mixer or equipment with same function, adding magnesium stearate, and mixing.
5. And (3) pressing the mixed granules into tablets, coating by using Opadry, wherein the average main pressure of the tablet press is controlled to be 5.0-11.0 KN during tabletting, the tabletting rotating speed is set to be less than or equal to 30.0rpm, sampling is carried out to check the properties, weight difference, hardness and friability of the tablet cores, the quality of the tablet cores is confirmed to meet the requirements, and tabletting is carried out according to the confirmed tabletting parameters.
Example 2
The embodiment discloses a pharmaceutical composition for treating angina pectoris, the dosage form of the pharmaceutical composition is a sustained-release tablet, and the pharmaceutical composition comprises the following components:
the preparation process comprises the following steps:
1. the ranolazine, microcrystalline cellulose and ethyl methacrylate copolymer in the formula are uniformly mixed by a high-speed granulator.
2. Dissolving sodium hydroxide in purified water, adding into the above uniformly mixed materials, stirring, and granulating.
3. Drying at 60 deg.C to obtain sustained release granule.
4. Grinding Borneolum Syntheticum and pulvis Talci, adding into the above delayed release granule, mixing with three-dimensional mixer or equipment with same function, adding magnesium stearate, and mixing.
5. The mixed granules were compressed into tablets and coated with opadry.
Example 3
The embodiment discloses a pharmaceutical composition for treating angina pectoris, the dosage form of the pharmaceutical composition is a sustained-release capsule, and the preparation consists of the following components:
| composition (I) | Dosage/tablet |
| Ranolazine | 300mg |
| Borneol (borneol) | 37.5mg |
| Microcrystalline cellulose | 42mg |
| Ethyl methacrylate copolymer | 40mg |
| Hydroxypropyl methylcellulose | 8mg |
| Sodium hydroxide | 1.5mg |
| Magnesium stearate | 8.5mg |
| Talcum powder | 37.5mg |
| Purified water | 0.15mg |
The preparation process comprises the following steps:
1. the ranolazine, microcrystalline cellulose and ethyl methacrylate copolymer in the formula are uniformly mixed by a high-speed granulator.
2. Dissolving sodium hydroxide in purified water, adding into the above uniformly mixed materials, stirring, and granulating.
3. Drying at 60 deg.C to obtain sustained release granule.
4. Grinding Borneolum Syntheticum and pulvis Talci, adding into the above delayed release granule, mixing with three-dimensional mixer or equipment with same function, adding magnesium stearate, and mixing.
5. And filling the mixed material into hard capsules to obtain capsules.
Test data
The formulations prepared in examples 1-3 of the invention were tested for release profile using a suitable assay to simulate in vivo release conditions.
The dissolution test data of the drug-containing coated particles of examples 1-3 are shown in Table 1.
Table 1: data for the two drug release tests in examples 1-3 above
Results of pharmacodynamics experiments
1. Laboratory animals and groups
48 New Zealand rabbits weighing about 2kg were randomized into 6 groups of 8 rabbits each, and the groups were divided into model groups, blank groups, administration groups (low dose group, medium dose group, and high dose group), and model groups administered with high fat diet (cholesterol, egg yolk powder, lard) for 8 weeks to induce atherosclerosis, and at the same time, 1. mu.g/kg/d was injected into the ear vein from the 7 th week of molding to induce myocardial ischemia-induced angina pectoris.
2. Administration plan
Except for the model group, each group was administered in the following specific manner.
| Group of | Classes of pharmaceutical compositions | Dosage of drug | Remarks for note |
| Blank group | — | 0 | Normal feeding without making mould |
| Model set | — | 0 | High-fat feed and moulding |
| Single square group | Ranolazine | 80mg | High-fat feed and moulding |
| Low dose group | Ranolazine and borneol | 27mg+2.7mg | High-fat feed and moulding |
| Middle dose group | Ranolazine+ borneol | 40mg+4.0mg | High-fat feed and moulding |
| High dose group | Ranolazine and borneol | 56mg+5.6mg | High-fat feed and moulding |
3. Observation index
3.1 serum Nitric Oxide (NO), serum Endothelin (ET), serum lipid peroxide (MDA) and other related indexes
Note: comparison with model groups: p < 0.01, between-group comparison P > 0.05
3.2 Pituitrin-induced changes in Electrocardiogram T waves
Note and model group comparison: p < 0.01, between-group comparison P > 0.05
As shown in pharmacodynamic experimental results, the dosage of ranolazine serving as a main drug can be greatly reduced compared with that of a single component group, and the compound component group with the reduced dosage can effectively exert the treatment effect, so that the side effect caused by the dosage effect of the drug can be reduced.
Therefore, the pharmaceutical composition for treating angina pectoris disclosed by the invention has a remarkable clinical curative effect especially on unstable angina pectoris and stable angina pectoris, and can reduce the administration dosage and improve the drug potency, thereby greatly reducing the side effect of the drug.
From the foregoing it will be appreciated that, although specific embodiments of the disclosure have been described herein for purposes of illustration, various modifications or improvements may be made by those skilled in the art without departing from the spirit and scope of the disclosure, and that such modifications or improvements are intended to be within the scope of the appended claims.
Claims (10)
1. A pharmaceutical composition for treating angina pectoris comprises main drug and Borneolum Syntheticum, wherein the main drug is selected from ranolazine, ranolazine hydrochloride or pharmaceutically acceptable salt of ranolazine.
2. The pharmaceutical composition of claim 1, wherein the weight ratio of the base drug to borneol is 1:1 to 10:1, preferably 5:1 to 8:1, preferably the ranolazine pharmaceutically acceptable salt is selected from ranolazine hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate, glutamate or mixtures thereof.
3. The pharmaceutical composition of claim 1 or 2, further comprising a non-functional excipient selected from microcrystalline cellulose, ethyl methacrylate copolymer, hydroxypropyl methylcellulose, talc, magnesium stearate, opadry or mixtures thereof.
4. The pharmaceutical composition of any one of claims 1 to 3, wherein the pharmaceutical composition is a tablet or a capsule, preferably the tablet is a sustained release tablet, preferably the capsule is a sustained release capsule.
5. A preparation method of a pharmaceutical composition for treating angina pectoris comprises the following steps:
mixing a main drug, microcrystalline cellulose and an ethyl methacrylate copolymer to obtain a mixture;
dissolving the mixture in an alkali solution to obtain sustained-release granules; and
mixing borneol, talcum powder and magnesium stearate with the sustained-release granules to obtain the pharmaceutical composition.
6. The preparation method of the pharmaceutical composition according to claim 5, wherein the main drug is selected from ranolazine, ranolazine hydrochloride or a pharmaceutically acceptable salt of ranolazine, preferably the weight ratio of the main drug to borneol is 1:1 to 10:1, preferably 5:1 to 8:1, preferably the pharmaceutically acceptable salt of ranolazine is selected from ranolazine hydrochloride, sulfate, hydrobromide, citrate, succinate, phosphate, lactate, pyruvate, acetate, benzenesulfonate, p-benzenesulfonate, glutamate or a mixture thereof, preferably the alkaline solution is selected from sodium hydroxide solution, potassium carbonate solution, sodium carbonate solution, potassium bicarbonate solution, sodium methoxide solution, sodium ethoxide solution or a mixture thereof.
7. The process for the preparation of a pharmaceutical composition according to claim 5 or 6, wherein the mixture is mixed by a high speed granulator, preferably for a mixing time of 5 to 8min, preferably the mixture is dissolved in an alkaline solution and then comprises a stirring step, preferably for a stirring time of 3 to 5min, preferably the mixture is granulated and then comprises a drying step, preferably the drying temperature is 30 ℃ to 100 ℃, more preferably 40 ℃ to 80 ℃, even more preferably 60 ℃, preferably the drying time is 30 to 50min, or the moisture content of the granules is controlled to be less than or equal to 3.0%.
8. The preparation method of the pharmaceutical composition according to claims 1 to 7, wherein the particle size of more than 70% of the sustained-release particles in the sustained-release particles is 20 to 80 mesh.
9. The process for the preparation of a pharmaceutical composition according to any one of claims 5 to 8, wherein the pharmaceutical composition is a tablet or a capsule, preferably a tablet is a sustained release tablet, preferably a capsule is a sustained release capsule.
10. A process for the preparation of a pharmaceutical composition according to claim 9, further comprising coating the tablet, preferably with opadry.
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| WO2023045740A1 (en) * | 2021-09-27 | 2023-03-30 | 天士力医药集团股份有限公司 | Pharmaceutical composition for treating myocardial ischemia and preparation method therefor |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| WO2023045740A1 (en) * | 2021-09-27 | 2023-03-30 | 天士力医药集团股份有限公司 | Pharmaceutical composition for treating myocardial ischemia and preparation method therefor |
| GB2613736A (en) * | 2021-09-27 | 2023-06-14 | Tasly Pharmaceutical Group Co | Pharmaceutical composition for treating myocardial ischemia and preparation method therefor |
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Address after: 219 Furong Zhongsi Road, Xishan Economic and Technological Development Zone, Wuxi City, Jiangsu Province, 214000 Applicant after: Zhuohe Pharmaceutical Group Co.,Ltd. Address before: 219 Furong Zhongsi Road, Xishan Economic and Technological Development Zone, Wuxi City, Jiangsu Province, 214000 Applicant before: Zhuohe Pharmaceutical Group Co.,Ltd. |
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Application publication date: 20200324 |