CN104971040B - A kind of fenoldopam mesylate injection and preparation method thereof - Google Patents
A kind of fenoldopam mesylate injection and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, and in particular to a kind of fenoldopam mesylate injection and preparation method thereof.The parenteral solution is mainly added to 1000 parts and formed by 8 12 parts of Fenoldopam Mesylate, 120 240 parts of propane diols, 0.8 3.6 parts of organic acid, 2.4 6 parts of antioxidant, 0.8 3.6 parts of pH adjusting agent, dilution, and the particle diameter of the Fenoldopam Mesylate is 10 μm ~ 100 μm.Solubility height, the steady quality of Fenoldopam Mesylate in the fenoldopam mesylate injection, the drug effect of Fenoldopam Mesylate can be fully played, it is a kind of injection of preferably treatment severe hypertension disease beneficial to preservation and the parenteral solution stability is high.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of fenoldopam mesylate injection and preparation method thereof.
Background technology
Hypertension is one of most common angiocardiopathy, and the disease that number of patients is most in the world.General blood pressure
Measured value is just hypertension higher than 140/90 millimetres of mercury, is shown according to newest research report, global hyperpietic is
Exceed 1,000,000,000, it is contemplated that to before 2025, the whole world there will be 15.6 hundred million people to suffer from this disease.Hypertension in China adult at present
For illness rate up to 33.5%, hyperpietic's number has breached 3.3 hundred million, i.e., just has a people to suffer from hypertension in every 3 adults.Cause
This, researching and developing out a kind of medicine that can effectively treat hypertension has highly important social effect and clinical meaning
Justice.
Fenoldopam Mesylate is the mesylate of fenoldopam, is a kind of vasodilator of snap action.Methanesulfonic acid
Fenoldopam is a kind of dopamine 1（DA1）Receptor stimulating agent, its major function are to stimulate DA1 receptor-inducible arteriolar dilatations, and
Reach reduction angiosthenia, increase the effect of renal hemodynamic.In addition, Fenoldopam Mesylate may also act on kidney cellule, have
Directly promote the characteristic of natruresis and diuresis, be a kind of Small side effects, be depressured fast hypertension drug.
In recent years, there are some researches show fenoldopam mesylate injection is to severe hypertension（Diastolic pressure >=16kPa）Patient
Dosage correlation angiosthenia caused by perfusion was reduced up to 24 hours, is had no the adverse reaction in terms of tolerance, is also had no drug withdrawal
Rebound phenomenon and obvious changes in heart rate, it is a kind of safe, Small side effects hypertension drug.Meanwhile the non-promise of sulfonic acid is more
Diazepam injection liquid has its renal function of improvement to some severe hypertensions with the patient of kidney function damage, and reduction receives heart or the non-heart
The Postoperative hypertension of dirty surgical patient, the effect of maintaining or increase urination amount, to severe hypertension with kidney function damage
Patient has good therapeutic action.
Fenoldopam Mesylate injection is due to curative effect is reliable, safe, decompression is fast, half-life short, will not lead
Cause unwanted blood pressure reduce the advantages of and be widely used in the treatment of high blood pressure disease.Chinese patent CN100356924C is disclosed
A kind of Phenoduopan methanesulphonate medicinal composition and its method for preparation, the Phenoduopan methanesulphonate medicinal composition are by first sulphur
Sour fenoldopam is prepared from the different acidic materials pharmacologically allowed, clear solution is made, then by lyophilized technique
It is freeze-dried, Fenoldopam Mesylate freeze drying powder injection is made.But freeze drying powder injection preparation technology has processing step
The shortcomings that more, technological parameter is difficult to control, and freeze-drier is complicated, cost is high, is unfavorable for the Fenoldopam Mesylate freeze-dried powder
The promotion and application of agent.
Therefore, research and develop that a kind of stability is good, preparation technology is simple, the low non-promise of the methanesulfonic acid low with side effect of cost
More diazepam injection agent are the problems of current urgent need to resolve.
The content of the invention
In order to overcome prior art Fenoldopam Mesylate freeze drying powder injection to exist, processing step is more, technological parameter is not easily-controllable
System, the shortcomings that freeze-drier is complicated, cost is high, it is an object of the invention to provide a kind of fenoldopam mesylate injection and its system
Preparation Method, to solve the above problems.
A kind of fenoldopam mesylate injection provided by the invention includes following components and its parts by weight：
Fenoldopam Mesylate 8-12 parts, propane diols 120-240 parts, organic acid 0.8-3.6 parts, antioxidant 2.4-6 parts,
PH adjusting agent 0.8-3.6 parts, dilution add to 1000 parts.
Further, the component of fenoldopam mesylate injection provided by the invention and its parts by weight are preferably
10 parts of Fenoldopam Mesylate, 150 parts of propane diols, 2 parts of organic acid, 4 parts of antioxidant, 2 parts of pH adjusting agent, dilution
Liquid adds to 1000 parts.
Further, the particle diameter of the Fenoldopam Mesylate is 10 μm ~ 100 μm, the grain of the Fenoldopam Mesylate
Footpath is preferably 30 μm -60 μm.
Further, the organic acid be tartaric acid, malic acid, citric acid, citric acid and maleic acid in one kind or its
Composition.
Further, the antioxidant is one kind or its composition in sodium pyrosulfite and sodium hydrogensulfite.
Further, the pH adjusting agent is one kind in sodium dihydrogen phosphate, sodium citrate and natrium malicum or its combination
Thing.
Further, the dilution is 0.9% sodium chloride solution or 5% glucose solution.
Further, the pH value of the fenoldopam mesylate injection is 3.4 ~ 4.4.
Because the solubility of Fenoldopam Mesylate in aqueous is relatively low, direct drug injection is extremely difficult to required for clinic
The concentration of Fenoldopam Mesylate, so as to influence the therapeutic effect of Fenoldopam Mesylate medicine.The present invention is by controlling first sulphur
The particle diameter of sour fenoldopam improves the solubility of Fenoldopam Mesylate, is found by substantial amounts of experimental study, and particle size range is
10 μm ~ 100 μm of Fenoldopam Mesylate can greatly improve its solubility in aqueous, the grain of Fenoldopam Mesylate
When footpath is more preferably 30 μm -60 μm, its solubility more preferably, solves the low problem of Fenoldopam Mesylate solubility.
In addition, fenoldopam mesylate injection provided by the invention with the addition of propane diols and organic acid, can be further
Raising Fenoldopam Mesylate solubility in aqueous, the fenoldopam mesylate injection is also protected at low temperature
Hold clear and bright state.In addition, the present invention is 3.4 ~ 4.4 by the pH value for adjusting parenteral solution, the non-promise of methanesulfonic acid can be effectively improved
The stability dissolved more, tests prove that, the fenoldopam mesylate injection is 25 DEG C ± 2 DEG C in temperature, relative humidity 60
Indices meet standard in 12 months in the environment of ± 10%, are advantageous to the preservation of the fenoldopam mesylate injection.
In addition, present invention also offers a kind of preparation method of fenoldopam mesylate injection, comprise the following steps：
Fenoldopam Mesylate is added in dilution and dissolved, propane diols is subsequently added into, stirs, add organic
Acid, antioxidant and pH adjusting agent, pH value is adjusted, decolourized, be sterile filtered, be sub-packed in cillin bottle, produce.
The preparation method step of fenoldopam mesylate injection provided by the invention is simple, does not need complicated production to set
It is standby, it is easily operated, be advantageous to the industrialized production of the fenoldopam mesylate injection.
In a word, fenoldopam mesylate injection provided by the invention, compared with prior art with following advantage：
1）Fenoldopam mesylate injection provided by the invention improves first by controlling the particle diameter of Fenoldopam Mesylate
The solubility of sulfonic acid fenoldopam, the drug effect of Fenoldopam Mesylate can be more fully played, improve Fenoldopam Mesylate
To the therapeutic effect of severe hypertension disease；
2）Fenoldopam mesylate injection provided by the invention has the advantages of steady quality, safe, is advantageous to
The promotion and application of the fenoldopam mesylate injection；
3）The preparation method of fenoldopam mesylate injection provided by the invention is simple, production cost is low, easily operated,
Be advantageous to the industrialized production of the fenoldopam mesylate injection.
Embodiment
The present invention is further described below by way of specific embodiment, the present invention is not limited only to following examples.In this hair
In bright scope or do not departing from present disclosure, in spirit and scope, the change that is carried out to the present invention, combining or replace
Change, will be apparent to the person skilled in the art, and be included within the scope of the present invention.
Embodiment 1, fenoldopam mesylate injection
The component of fenoldopam mesylate injection：
Fenoldopam Mesylate 8g, propane diols 80g, citric acid 0.8g, sodium pyrosulfite 2.4g, sodium dihydrogen phosphate 0.8g,
Add 0.9% sodium chloride solution that 1ml specifications are made, make 1000 altogether, described Fenoldopam Mesylate to 1000ml
Particle diameter is 10 μm ~ 100 μm.
Its preparation method comprises the following steps：
The Fenoldopam Mesylate 8g for weighing recipe quantity is suspended in the sodium chloride solutions of 500 ml 0.9%, adds the third two
Alcohol 80g, stirring is completely dissolved it, then is separately added into the citric acid 0.8g, sodium pyrosulfite 2.4g, sodium dihydrogen phosphate of recipe quantity
0.6g, 0.9% sodium chloride solution is added to continue stirring to 1000ml to dissolving, add appropriate activated carbon, stir 20min, use
0.45um membrane filtration decarburizations, filling, 1ml/ branch, inflated with nitrogen sealing, sterilizing, leak detection, lamp inspection, are produced.
Embodiment 2, fenoldopam mesylate injection
The component of fenoldopam mesylate injection：
Fenoldopam Mesylate 10g, propane diols 150g, malic acid 2g, sodium hydrogensulfite 4g, natrium malicum 3g plus 5% Portugal
Grape sugar juice is made 1ml specifications, makes 1000 altogether, described Fenoldopam Mesylate particle diameter is 10 μm ~ 100 μm to 1000ml.
Its preparation method comprises the following steps：
The Fenoldopam Mesylate 10g for weighing recipe quantity is suspended in the glucose solutions of 500 ml 5%, adds propane diols
150g, stirring is completely dissolved it, then is separately added into the malic acid 0.8g, sodium sulfite 4g, natrium malicum 0.8g of recipe quantity, adds
5% glucose solution continues stirring to dissolving, adds appropriate activated carbon, 20min is stirred, with 0.45um filter membrane mistakes to 1000ml
Decarburization is filtered, filling, 1ml/ branch, inflated with nitrogen sealing, sterilizing, leak detection, lamp inspection, is produced.
Embodiment 3, fenoldopam mesylate injection
The component of fenoldopam mesylate injection：
Fenoldopam Mesylate 120g, propane diols 2400g, citric acid 36g, sodium pyrosulfite 60g, natrium malicum 24g,
0.9% sodium chloride solution adds to 1000ml, and 1ml specifications are made, and makes 1000 altogether, described Fenoldopam Mesylate
Particle diameter is 10 μm ~ 100 μm.
Its preparation method comprises the following steps：
The Fenoldopam Mesylate 120g for weighing recipe quantity is suspended in the sodium chloride solutions of 500ml 0.9%, adds the third two
Alcohol 2400g, stirring is completely dissolved it, then is separately added into the citric acid 36g, sodium pyrosulfite 60g, natrium malicum of recipe quantity
8g, 0.9% sodium chloride solution is added to continue stirring to 1000ml to dissolving, add appropriate activated carbon, stir 20min, use
0.45um membrane filtration decarburizations, filling, 1ml/ branch, inflated with nitrogen sealing, sterilizing, leak detection, lamp inspection, are produced.
The solubility test of test example one, Fenoldopam Mesylate
1st, test material：The methanesulfonic acid of Fenoldopam Mesylate powder, particle diameter less than 10 μm that particle diameter is 10 μm ~ 100 μm
The Fenoldopam Mesylate powder of fenoldopam powder, particle diameter more than 100 μm, propylene glycol solution, 0.9% sodium chloride solution and 5%
Glucose solution.
2nd, test method：Press《Two note on the use solubility test methods of China's coastal port》It is more to carry out the non-promise of methanesulfonic acid
The solubility test dissolved, 9 beakers are taken, be divided into 3 groups, every group of beaker is denoted as sample 1, sample 2 and sample 3, the burning of sample 1
Cup all adds the Fenoldopam Mesylate powder that 1g particle diameters are 10 μm ~ 100 μm, and the beaker of sample 2 all adds 1g particle diameters and is less than 10 μ
M Fenoldopam Mesylate powder, the beaker of sample 3 all add the Fenoldopam Mesylate powder that 1g particle diameters are more than 100 μm, so
The propylene glycol solution, 0.9% sodium chloride solution and 5% glucose solution of certain volume are separately added into afterwards to Fenoldopam Mesylate powder
Untill end is completely dissolved, the addition of above-mentioned 3 kinds of solution is recorded to judge the solubility of Fenoldopam Mesylate powder, judges to mark
It is accurate as follows：
3rd, result of the test：
Result of the test is as shown in table 1.
The solubility test of the Fenoldopam Mesylate of table 1
As shown in Table 1, solubility of the sample 1 in propylene glycol solution, 0.9% sodium chloride solution and 5% glucose solution is equal
Solubility than sample 2 and sample 3 is big, illustrates that the Fenoldopam Mesylate that particle diameter provided by the invention is 10 μm ~ 100 μm has
Higher solubility.
The stability test of test example two, fenoldopam mesylate injection
1st, test material：Fenoldopam mesylate injection prepared by embodiment 2.
2nd, test method：Fenoldopam mesylate injection prepared by embodiment 2 is placed on temperature as 25 DEG C ± 2 DEG C,
Relative humidity is in 60 ± 10% environment, respectively at 0th month, 1 month, 3 months, 6 months, 9 months, 12 the end of month detections
Outward appearance, pH value and the changes of contents of Fenoldopam Mesylate injection.
3rd, result of the test：
Result of the test is as shown in table 2.
The stability test of the fenoldopam mesylate injection of table 2
Drawn by the data of table 2, fenoldopam mesylate injection prepared by the present invention, be 25 DEG C ± 2 DEG C in temperature, relatively
Indices meet standard in 12 months in the environment that humidity is 60 ± 10%, illustrate the Fenoldopam Mesylate injection of the present invention
Liquid stability is high, is advantageous to industrialized production and the application of the fenoldopam mesylate injection.
Claims (6)
1. a kind of fenoldopam mesylate injection, it is characterised in that including following components and its parts by weight：
Fenoldopam Mesylate 8-12 parts, propane diols 120-240 parts, organic acid 0.8-3.6 parts, antioxidant 2.4-6 parts, pH are adjusted
Section agent 0.8-3.6 parts, dilution add to 1000 parts, and the particle diameter of the Fenoldopam Mesylate is 10 μm~100 μm, the first sulphur
The pH value of sour fenoldopam parenteral solution is 3.4~4.4.
2. fenoldopam mesylate injection as claimed in claim 1, it is characterised in that including following components and its parts by weight
Number：
10 parts of Fenoldopam Mesylate, 150 parts of propane diols, 2 parts of organic acid, 4 parts of antioxidant, 2 parts of pH adjusting agent, dilution add
To 1000 parts.
3. fenoldopam mesylate injection as claimed in claim 1 or 2, it is characterised in that the organic acid be tartaric acid,
One kind or its composition in malic acid, citric acid, citric acid and maleic acid.
4. fenoldopam mesylate injection as claimed in claim 1 or 2, it is characterised in that the antioxidant is burnt sub-
One kind or its composition in sodium sulphate and sodium hydrogensulfite.
5. fenoldopam mesylate injection as claimed in claim 1 or 2, it is characterised in that the pH adjusting agent is phosphoric acid
One kind or its composition in sodium dihydrogen, sodium citrate and natrium malicum.
6. fenoldopam mesylate injection as claimed in claim 1 or 2, it is characterised in that the dilution is 0.9% chlorine
Change sodium solution or 5% glucose solution.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1830446A (en) * | 2006-04-14 | 2006-09-13 | 中国药科大学 | Phenoduopan methanesulphonate medicinal composition and its preparation |
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| US8859001B2 (en) * | 2007-10-18 | 2014-10-14 | Mia Levite | Fenoldopam formulations and pro-drug derivatives |
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| CN1830446A (en) * | 2006-04-14 | 2006-09-13 | 中国药科大学 | Phenoduopan methanesulphonate medicinal composition and its preparation |
Non-Patent Citations (1)
| Title |
|---|
| "Center for drug evalution and research，Clinical pharmacology and biopharmaceutics review NDA19922，Corlopam";Abbott Laboratories;《Center for drug evalution and research，Clinical pharmacology and biopharmaceutics review》;20040308;参见第22页和第35页 * |
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