CN105169409A - Compound of propranolol or medicinal salt thereof and ion exchange resin and suspension of compound - Google Patents
Compound of propranolol or medicinal salt thereof and ion exchange resin and suspension of compound Download PDFInfo
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- CN105169409A CN105169409A CN201510699027.9A CN201510699027A CN105169409A CN 105169409 A CN105169409 A CN 105169409A CN 201510699027 A CN201510699027 A CN 201510699027A CN 105169409 A CN105169409 A CN 105169409A
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Abstract
The invention relates to a compound of propranolol or a medicinal salt thereof and ion exchange resin and a preparation method of the compound. The compound comprises propranolol and a salt thereof and ion exchange resin, wherein the ion exchange resin is selected from one or more of polacrilin (polacrilin), polacrilin potassium (polacrilin potassium) and sodium polystyrenesulfonate. The compound of the propranolol and the salt thereof provided by the invention can be further prepared into an oral preparation, especially an oral suspension; the bitter taste and the thrill of a propranolol medicine solution can be removed; meanwhile, the stability of the compound is greatly improved; harmful impurities are reduced when the taking compliance is improved; the product quality is improved; and the medication safety of a patient is ensured.
Description
Technical field
The present invention relates to complex and the suspension thereof of Propranolol or its officinal salt and ion exchange resin, belong to field of pharmaceutical preparations.
Background technology
Infant hemangioma (infantilehemangioma, IH) is the modal benign tumor of infantile period.During birth, angiomatous sickness rate is 1.1% ~ 2.6%, and in 1 years old, sickness rate can up to 10% ~ 12%.The hemangioma of 85% ~ 90% can spontaneous regression, without the need to special treatment, but part-blood tuberculation growth site may affect attractive in appearance, affect body function even threat to life, need active treatment.Traditional Therapeutic Method is a lot, as freezing, isotope sticks, laser, Drug therapy, excision skin-grafting etc., all have certain therapeutic effect, but the side effect all existed in various degree or an Operative risk.
After reported first oral propranolol in 2008 is used for the treatment of IH, the treatment for IH provides new thinking.Subsequently, a large amount of clinical practices confirms that propranolol in treatment hemangioma is rapid-action, and determined curative effect, individual variation is little, and in normal dosage range, Propranolol untoward reaction is few.
For infant oral formulations, adopt oral liquid can improve its compliance of taking medicine.But the bitter in the mouth of Propranolol own, have intense stimulus, take rear oral cavity and produce feeling of numbness for a long time, solution is to light sensitive, and the exploitation of these features to its oral liquid of Propranolol causes certain difficulty simultaneously.Disclose a kind of Propranolol aqueous solution not containing alcohol containing non-sugar-type sweeting agent in CN102405041A, form consistent product with its prescription, developed by French PierreFabre, and in U.S.'s listing, commodity are called HEMANGEOL
tM, be used for the treatment of the medicine of infant hemangioma hypertrophy.Though this product adds a large amount of correctivess and sweeting agent, the bitterness of Propranolol is still obvious, and the feeling of numbness taking rear oral cavity is obvious, and places 10 days under illumination condition, and solution colour deepens, and related substance increases.
If Propranolol is prepared into oral liquid, physics is adopted to add the method for correctives and sweeting agent, be difficult to reach and cover Propranolol bitterness, improve the object of its stability, and the zest taking rear oral cavity can not be improved, therefore need to adopt suitable method to reach taste masking, to solve the feeling of numbness the object improving stability of taking rear oral cavity simultaneously.
Summary of the invention
In order to overcome the deficiency of Propranolol oral liquid, Propranolol or its officinal salt and ion exchange resin are formed complex by the present invention, it is large that this complex has drug loading, effectively eliminate bitterness and the zest of Propranolol in oral administration mixed suspension, solve the feeling of numbness taking rear oral cavity, and improve its stability, and this complex preparation method is simple, is easy to suitability for industrialized production simultaneously.
One aspect of the present invention provides a kind of Propranolol complex, and wherein, described complex comprises Propranolol or its officinal salt and ion exchange resin.Preferably, described complex is made up of Propranolol or its officinal salt and ion exchange resin.
In the present invention, preferred ion exchanger resin is selected from the mixture of one or more the arbitrary proportion in polacrilin (i.e. polacrilin), polacrilin potassium (i.e. polacrilin potassium), kayexalate.More preferably, ion exchange resin is the mixture of the arbitrary proportion of polacrilin, polacrilin potassium, polacrilin and polacrilin potassium, polacrilin potassium and the mixture of arbitrary proportion of kayexalate or the mixture of the arbitrary proportion of polacrilin, polacrilin potassium and kayexalate.Most preferably, ion exchange resin is polacrilin potassium.
In the present invention, the officinal salt of preferred Propranolol is selected from one or more in hydrochlorate, sulfate, hydrobromate, hydriodate, phosphate, nitrate, maleate, lactate, fumarate, citrate, formates, benzoate, acetate, trifluoroacetate, mesylate, esilate, benzene sulfonate, toluene fulfonate, succinate, citrate, Salicylate, Ascorbate; More preferably, the officinal salt of Propranolol is selected from one or more in hydrochlorate, sulfate, maleate, lactate, fumarate, citrate; Most preferably, the officinal salt of Propranolol is hydrochlorate.
In preferred embodiments, in complex, the mass ratio of Propranolol or its officinal salt and ion exchange resin is 4:1 ~ 1:4, more preferably 2:1 ~ 1:2, most preferably from about 1:1.
Another aspect of the present invention provides the preparation method of above-mentioned Propranolol complex, Propranolol or its officinal salt is comprised the steps: to be dissolved in solvent, add ion exchange resin, stir until ion exchange reaches balance, obtain the solution containing complex.Preferably, further by solid-liquid separation, drying is carried out to solid, obtain complex dry product.
In above-mentioned preparation method, solvent can be any solvent that can dissolve Propranolol or its officinal salt, is preferably water, most preferably is purified water.
In preferred embodiments, the amount ratio of Propranolol or its officinal salt and ion exchange resin is 4:1 ~ 1:4, more preferably 2:1 ~ 1:2, most preferably from about 1:1.
In above-mentioned preparation method, alr mode and mixing time are not particularly limited, this area can various alr modes be all suitable for the present invention, mixing time is until ion exchange reaches balance (namely free drug amount reaches constant).Preferably, mixing time at least 5 minutes, preferably 15 minutes ~ 4 hours further, further preferably 0.5 ~ 2 hour, most preferably from about 1 hour.This area can various solid-liquid separating method and drying means be all suitable for the present invention.
Complex of the present invention can be used for preparing medicine, such as, can add various adjuvant well known by persons skilled in the art further and make various suitable preparation, preferred oral preparation, include but not limited to the dosage forms such as oral administration mixed suspension, oral cavity disintegration tablet, dispersible tablet, slow releasing tablet.
The present invention another aspect provides a kind of oral administration mixed suspension, wherein adds Propranolol complex of the present invention.Preferably, in every 100 milliliters of suspensions, add Propranolol complex of the present invention 0.125 ~ 10.0g, further preferably 0.3 ~ 4.5g, more preferably 0.45 ~ 3.0g, most preferably 0.45 ~ 1.8g.
Invention further provides a kind of oral administration mixed suspension, wherein comprise Propranolol or its officinal salt, and ion exchange resin.Preferably, Propranolol or its officinal salt 0.1 ~ 2.0g, ion exchange resin 0.025 ~ 8.0g is contained in every 100 milliliters of suspensions; Preferred Propranolol or its officinal salt 0.2 ~ 1.5g, ion exchange resin 0.1 ~ 3.0g further; More preferably Propranolol or its officinal salt 0.3 ~ 1.0g, ion exchange resin 0.15 ~ 2.0g; Most preferably Propranolol or its officinal salt 0.3 ~ 0.6g, ion exchange resin 0.15 ~ 1.2g.
In the present invention, surfactant is comprised further in preferred oral suspension.Preferably, the various surfactants that surfactant can use this area conventional, be preferably selected from polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, fatty acid esters of sorbitan, polyoxyethylene fatty acid alcohol ether, poloxalkol one or more.Preferably, surfactant 0.001g ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 1.0g in every 100 milliliters of suspensions.
In the present invention, preferred oral suspension comprises one or more in suspending agent, correctives, antiseptic, coloring agent, pH value regulator further.
In the present invention, the various suspending agents that suspending agent can use this area conventional, be preferably selected from hypromellose, hyprolose, hydroxyethyl-cellulose, methylcellulose, sodium carboxymethyl cellulose, glycerol, propylene glycol, sorbitol, maltose alcohol, xanthan gum, tragakanta one or more.Preferably, suspending agent 0.001 ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 1.0g in every 100 milliliters of suspensions.
In the present invention, the various correctivess that correctives can use this area conventional, be preferably selected from saccharin sodium, menthol, cherry essence, vanilla, strawberry essence, fragrant citrus essence one or more.Preferably, correctives 0.001 ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 0.5g in every 100 milliliters of suspensions.
In the present invention, the various antiseptic that antiseptic can use this area conventional, be preferably selected from methyl hydroxybenzoate, ethyl hydroxybenzoate, butoben one or more.Preferably, antiseptic 0 ~ 1.0g is comprised, more preferably 0.05 ~ 0.5g, most preferably 0.1 ~ 0.3g in every 100 milliliters of suspensions.
In the present invention, the various coloring agent that coloring agent can use this area conventional, are preferably selected from yellow No. 6 of blue berry color pigment, FD & C, any one or more of red No. 33 of red No. 3 of FD & C, D & C.Preferably, contain toner 0.0005-0.1g, more preferably 0.001-0.05g, most preferably 0.005-0.02g in every 100 milliliters of suspensions.
In the present invention, the various pH value regulator that pH value regulator can use this area conventional, are preferably selected from one or more of the organic acid such as citric acid, sodium citrate, tartaric acid, sodium tartrate, lactic acid, sodium lactate and salt thereof.The pH value range of preferred oral suspension is 5 ~ 10, preferably 6 ~ 9, more preferably 6 ~ 8, most preferably from about 7.
The present invention another aspect provides a kind of preparation method of oral administration mixed suspension, comprises the following steps: be scattered in water by Propranolol complex of the present invention, stir.
Invention further provides a kind of preparation method of oral administration mixed suspension, comprise the following steps: Propranolol or its officinal salt are dissolved in the water, add ion exchange resin, stir until ion exchange reaches balance.In this preparation method, alr mode and mixing time are not particularly limited, this area can various alr modes be all suitable for the present invention, mixing time is until ion exchange reaches balance (namely free drug amount reaches constant).Preferred stirring at least 5 minutes, preferably 15 minutes ~ 4 hours further, further preferably 0.5 ~ 2 hour, most preferably from about 1 hour.
In the present invention, the preparation method of preferred oral suspension comprise the steps: to add in surfactant, suspending agent, correctives, antiseptic, coloring agent, pH adjusting agent further one or more, stir.Preferred water is purified water.
Medicine prepared by Propranolol complex of the present invention, such as oral administration mixed suspension of the present invention, can be used for the diseases such as treatment infant hemangioma, arrhythmia, angina pectoris, hypertension, pheochromocytoma.
Propranolol complex of the present invention, eliminate bitterness and the zest of Propranolol, after making medicine such as oral administration mixed suspension of the present invention, because taste masking is effective, and solve the feeling of numbness taking rear oral cavity, improve patient's particularly infant patient's compliance of taking medicine.In addition, the complex of Propranolol and ion exchange resin also substantially increases the stability of medicine such as oral administration mixed suspension of the present invention, can reduce the generation of objectionable impurities, improve the quality of products, and ensures the safety of patient medication.For infant hemangioma patient, prepare oral compliance good, quality controllable, stable Propranolol oral liquid, is conducive to the promotion and application clinically of this product.
Accompanying drawing explanation
Fig. 1: comparative example 1 propranolol hydrochloride solution illumination 10 days chromatograms.
Fig. 2: commercially available product illumination 10 days chromatograms.
Fig. 3: embodiment 1 propranolol hydrochloride and polacrilin complex solution illumination 10 days chromatograms.
Fig. 4: embodiment 2 propranolol hydrochloride and polacrilin potassium complex solution illumination 10 days chromatograms.
Fig. 5: embodiment 3 propranolol hydrochloride and kayexalate complex solution illumination 10 days chromatograms.
Fig. 6: embodiment 8 propranolol hydrochloride complex oral administration mixed suspension illumination 10 days chromatograms.
Detailed description of the invention
The present invention is described in detail by following embodiment, but those skilled in the art understand, and protection scope of the present invention does not limit to embodiment therewith, and any improvement of making on basis of the present invention and change, all within protection scope of the present invention.
The reagent used in the embodiment of the present invention and instrument if no special instructions, are commercial goods.Adjuvant if no special instructions, is pharmaceutical grade product.
Embodiment 1
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin of recipe quantity, stirs 1 hour, to obtain final product.
Embodiment 2
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, to obtain final product.
Embodiment 3
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the kayexalate of recipe quantity, stirs 1 hour, to obtain final product.
Embodiment 4
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, to obtain final product.
Embodiment 5
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, to obtain final product.
Embodiment 6
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, is filtered by suspension solution, collects complex, in 60 DEG C of dryings 1 hour, obtains complex dry product.
Embodiment 7
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, is filtered by suspension solution, collects complex, in 60 DEG C of dryings 1 hour, obtains complex dry product.
Comparative example 1
Preparation technology: the purified water of getting recipe quantity, adds the propranolol hydrochloride of recipe quantity, stirring and dissolving, to obtain final product.
Test example 1
Experimental technique in the stability test research guideline of reference " Chinese Pharmacopoeia " 2010 editions two annex IXIJ chemical drugss and pharmaceutical preparation, sample prepared by Example 1-6 and comparative example 1 and commercially available product HEMANGEOL
tMcarry out stability test research, the results are shown in table 1.
Table 1: stability test is studied
From above-mentioned result of the test, the propranolol hydrochloride complex prepared according to the inventive method, compared with comparative example 1 and commercially available product, eliminate bitterness and the zest of drug solution, substantially increase its stability simultaneously, while its Compliance of raising, reduce the generation of objectionable impurities, improve the quality of products, ensure the safety of patient medication.
Embodiment 8
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride complex of recipe quantity, stirring makes dispersion, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 9
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 10
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 11
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the kayexalate of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 12
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 13
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 7.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 14
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, adds the polacrilin potassium of recipe quantity, stirs 1 hour, add pH value regulator adjust ph to 5.0, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Embodiment 15
Preparation technology: the purified water of getting recipe quantity 30%, add the propranolol hydrochloride of recipe quantity, stirring and dissolving, add the polacrilin potassium of recipe quantity, stir 1 hour, add surfactant, suspending agent, correctives, antiseptic, coloring agent, stir, add purified water to full dose, stir, to obtain final product.
Test example 2
Experimental technique in the stability test research guideline of reference " Chinese Pharmacopoeia " 2010 editions two annex IXIJ chemical drugss and pharmaceutical preparation, sample prepared by Example 8-15 and comparative example 1 and commercially available product HEMANGEOL
tMcarry out stability test research, the results are shown in table 2.
Table 2: stability test is studied
From above-mentioned result of the test, the propranolol hydrochloride oral administration mixed suspension prepared according to the inventive method, compared with comparative example 1 and commercially available product, eliminate bitterness and the zest of drug solution, substantially increase its stability simultaneously, while its Compliance of raising, reduce the generation of objectionable impurities, improve the quality of products, ensure the safety of patient medication.
In above-mentioned test example 1 and 2, the chromatographic results that comparative example 1, commercially available product, embodiment 1, embodiment 2, embodiment 3 and embodiment 8 are irradiated 10 days respectively sees the following form respectively, and chromatogram is shown in accompanying drawing 1-6 respectively.
Table 3: comparative example 1 propranolol hydrochloride solution illumination 10 days chromatographic results
Detector A292nm
| Peak number | Retention time | Area | Area % | Separating degree (USP) |
| 1 | 10.835 | 102345 | 0.355 | -- |
| 2 | 12.543 | 33838 | 0.117 | 3.855 |
| 3 | 13.795 | 17590 | 0.061 | 3.068 |
| 4 | 15.438 | 364776 | 1.264 | 3.812 |
| 5 | 18.831 | 55955 | 0.194 | 7.607 |
| 6 | 20.045 | 26938 | 0.093 | 2.595 |
| 7 | 21.089 | 15820 | 0.055 | 2.650 |
| 8 | 21.850 | 28242366 | 97.834 | 2.035 |
| 9 | 27.578 | 8035 | 0.028 | 12.902 |
| Amount to | 28867666 | 100.000 |
Table 4: commercially available product illumination 10 days chromatographic results
Detector ACh1292nm
| Peak # | Retention time | Area | Area % | Separating degree |
| 1 | 12.670 | 34025 | 0.104 | 0.000 |
| 2 | 17.163 | 26087 | 0.079 | 10.029 |
| 3 | 18.539 | 15473 | 0.047 | 4.040 |
| 4 | 19.833 | 210841 | 0.642 | 5.250 |
| 5 | 21.622 | 44116 | 0.134 | 9.829 |
| 6 | 24.806 | 32531401 | 98.994 | 10.321 |
| Amount to | 32861942 | 100.000 |
Table 5: embodiment 1 propranolol hydrochloride and polacrilin complex solution illumination 10 days chromatographic results
Detector ACh1292nm
| Peak # | Retention time | Area | Area % | Separating degree |
| 1 | 24.671 | 33643436 | 99.962 | 0.000 |
| 2 | 30.619 | 12900 | 0.038 | 16.533 |
| Amount to | 33656336 | 100.000 |
Table 6: embodiment 2 propranolol hydrochloride and polacrilin potassium complex solution illumination 10 days chromatographic results
Detector ACh1292nm
| Peak # | Retention time | Area | Area % | Separating degree |
| 1 | 24.679 | 34867615 | 99.962 | 0.000 |
| 2 | 30.635 | 13350 | 0.038 | 16.089 |
| Amount to | 34880965 | 100.000 |
Table 7: embodiment 3 propranolol hydrochloride and kayexalate complex solution illumination 10 days chromatographic results
Detector ACh1292nm
| Peak # | Retention time | Area | Area % | Separating degree |
| 1 | 24.693 | 33012788 | 99.963 | 0.000 |
| 2 | 30.661 | 12371 | 0.037 | 16.422 |
| Amount to | 33025159 | 100.000 |
Table 8: embodiment 8 propranolol hydrochloride complex oral administration mixed suspension illumination 10 days chromatographs
Detector ACh1292nm
| Peak # | Retention time | Area | Area % | Separating degree |
| 1 | 24.739 | 34233897 | 99.963 | 0.000 |
| 2 | 30.699 | 12581 | 0.037 | 16.126 |
| Amount to | 34246478 | 100.000 |
Claims (11)
1. a complex, is characterized in that, described complex comprises Propranolol or its officinal salt and ion exchange resin.
Preferably, described complex is made up of Propranolol or its officinal salt and ion exchange resin.
More preferably, the mass ratio of described Propranolol or its officinal salt and ion exchange resin is 4:1 ~ 1:4, preferred 2:1 ~ 1:2; Most preferably from about 1:1.
2. complex according to claim 1, is characterized in that, preferably, described ion exchange resin is selected from one or more the mixture in polacrilin, polacrilin potassium, kayexalate.More preferably, described ion exchange resin is the mixture of polacrilin, polacrilin potassium, polacrilin and polacrilin potassium, polacrilin potassium and the mixture of kayexalate or the mixture of polacrilin, polacrilin potassium and kayexalate.Most preferably, described ion exchange resin is polacrilin potassium.
Preferably, described officinal salt is selected from one or more in hydrochlorate, sulfate, hydrobromate, hydriodate, phosphate, nitrate, maleate, lactate, fumarate, citrate, formates, benzoate, acetate, trifluoroacetate, mesylate, esilate, benzene sulfonate, toluene fulfonate, succinate, citrate, Salicylate, Ascorbate; More preferably, described officinal salt is selected from one or more in hydrochlorate, sulfate, maleate, lactate, fumarate, citrate; Most preferably, described officinal salt is hydrochlorate.
3. the preparation method of the complex according to any one of claim 1-2, is characterized in that, comprises the steps: Propranolol or its officinal salt to be dissolved in solvent, adds ion exchange resin, stirs until ion exchange reaches balance.Preferably, comprise the steps: solid-liquid separation further, drying is carried out to solid.
Preferred described solvent is water, most preferably is purified water.
Preferably, the amount ratio of described Propranolol or its officinal salt and ion exchange resin is 4:1 ~ 1:4, more preferably 2:1 ~ 1:2, most preferably from about 1:1.
Preferred stirring at least 5 minutes, preferably 15 minutes ~ 4 hours further, further preferably 0.5 ~ 2 hour, most preferably from about 1 hour.
4. an oral administration mixed suspension, is characterized in that, wherein adds the complex according to any one of claim 1-2.
Preferably, in every 100 milliliters of suspensions, add the complex 0.125 ~ 10.0g according to any one of claim 1-2, further preferably 0.3 ~ 4.5g, more preferably 0.45 ~ 3.0g, most preferably 0.45 ~ 1.8g.
5. an oral administration mixed suspension, is characterized in that, wherein comprises Propranolol or its officinal salt, and ion exchange resin.Preferably, Propranolol or its officinal salt 0.1 ~ 2.0g, ion exchange resin 0.025 ~ 8.0g is comprised in every 100 milliliters of suspensions; Preferred Propranolol or its officinal salt 0.2 ~ 1.5g, ion exchange resin 0.1 ~ 3.0g further; More preferably Propranolol or its officinal salt 0.3 ~ 1.0g, ion exchange resin 0.15 ~ 2.0g; Most preferably Propranolol or its officinal salt 0.3 ~ 0.6g, ion exchange resin 0.15 ~ 1.2g.
Preferably, described ion exchange resin is selected from one or more the mixture in polacrilin, polacrilin potassium, kayexalate.More preferably, described ion exchange resin is the mixture of polacrilin, polacrilin potassium, polacrilin and polacrilin potassium, polacrilin potassium and the mixture of kayexalate or the mixture of polacrilin, polacrilin potassium and kayexalate.Most preferably, described ion exchange resin is polacrilin potassium.
Preferably, described officinal salt is selected from one or more in hydrochlorate, sulfate, hydrobromate, hydriodate, phosphate, nitrate, maleate, lactate, fumarate, citrate, formates, benzoate, acetate, trifluoroacetate, mesylate, esilate, benzene sulfonate, toluene fulfonate, succinate, citrate, Salicylate, Ascorbate; More preferably, described officinal salt is selected from one or more in hydrochlorate, sulfate, maleate, lactate, fumarate, citrate; Most preferably, described officinal salt is hydrochlorate.
6. the oral administration mixed suspension according to claim 4 or 5, is characterized in that, comprises surfactant further.
Preferably, described surfactant is selected from one or more in polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, fatty acid esters of sorbitan, polyoxyethylene fatty acid alcohol ether, poloxalkol.
Preferably, surfactant 0.001g ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 1.0g in every 100 milliliters of suspensions.
7. the oral administration mixed suspension according to any one of claim 4-6, is characterized in that, comprises one or more in suspending agent, correctives, antiseptic, coloring agent, pH value regulator further.
Preferably, described suspending agent is selected from one or more in hypromellose, hyprolose, hydroxyethyl-cellulose, methylcellulose, sodium carboxymethyl cellulose, glycerol, propylene glycol, sorbitol, maltose alcohol, xanthan gum, tragakanta.Preferably, suspending agent 0.001 ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 1.0g in every 100 milliliters of suspensions.
Preferably, described correctives is selected from one or more in saccharin sodium, menthol, cherry essence, vanilla, strawberry essence, fragrant citrus essence.Preferably, correctives 0.001 ~ 10.0g is comprised, more preferably 0.01 ~ 3.0g, most preferably 0.1 ~ 0.5g in every 100 milliliters of suspensions.
Preferably, described antiseptic is selected from one or more in methyl hydroxybenzoate, ethyl hydroxybenzoate, butoben.Preferably, antiseptic 0 ~ 1.0g is comprised, more preferably 0.05 ~ 0.5g, most preferably 0.1 ~ 0.3g in every 100 milliliters of suspensions.
Preferably, described coloring agent is selected from yellow No. 6 of blue berry color pigment, FD & C, one or more in red No. 33 of red No. 3 of FD & C, D & C.Preferably, contain toner 0.0005 ~ 0.1g, more preferably 0.001 ~ 0.05g, most preferably 0.005 ~ 0.02g in every 100 milliliters of suspensions.
Preferably, described pH value regulator is selected from one or more in citric acid, sodium citrate, tartaric acid, sodium tartrate, lactic acid, sodium lactate.Preferably, the pH value range of suspension is 5 ~ 10, preferably 6 ~ 9, more preferably 6 ~ 8, most preferably from about 7.
8. the preparation method of oral administration mixed suspension according to claim 4, is characterized in that, comprises the following steps: be scattered in water by described complex, stir.
9. the preparation method of oral administration mixed suspension according to claim 5, is characterized in that, comprises the following steps: Propranolol or its officinal salt are dissolved in the water, add ion exchange resin, stirs until ion exchange reaches balance.
Preferred stirring at least 5 minutes, preferably 15 minutes ~ 4 hours further, further preferably 0.5 ~ 2 hour, most preferably from about 1 hour.
10. preparation method according to claim 8 or claim 9, is characterized in that, comprises the steps: to add one or more in surfactant, suspending agent, correctives, antiseptic, coloring agent, pH value regulator further, stirs.Preferred described water is purified water.
The oral administration mixed suspension of 11. complex according to any one of claim 1-2 or any one of claim 4-7 is preparing the purposes in medicine.
Preferably, described medicine is oral formulations, is more preferably oral administration mixed suspension.More preferably, described medicine is used for the treatment of infant hemangioma, arrhythmia, angina pectoris, hypertension or pheochromocytoma.Also more preferably described medicine is used for the treatment of infant hemangioma.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510699027.9A CN105169409A (en) | 2015-10-25 | 2015-10-25 | Compound of propranolol or medicinal salt thereof and ion exchange resin and suspension of compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510699027.9A CN105169409A (en) | 2015-10-25 | 2015-10-25 | Compound of propranolol or medicinal salt thereof and ion exchange resin and suspension of compound |
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| CN105169409A true CN105169409A (en) | 2015-12-23 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115350152A (en) * | 2022-07-27 | 2022-11-18 | 武汉科福新药有限责任公司 | Propranolol sustained-release oral suspension and preparation method thereof |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102406616A (en) * | 2011-11-30 | 2012-04-11 | 上海景峰制药有限公司 | Montmorillonite combined propranolol sustained-release dry suspension, preparation method thereof and preparation method of Na-montmorillonite used in propranolol sustained-release dry suspension |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102406616A (en) * | 2011-11-30 | 2012-04-11 | 上海景峰制药有限公司 | Montmorillonite combined propranolol sustained-release dry suspension, preparation method thereof and preparation method of Na-montmorillonite used in propranolol sustained-release dry suspension |
Non-Patent Citations (2)
| Title |
|---|
| MONGKOL SRIWONGJANYA ET AL.: "Effect of ion exchange resins on the drug release from matrix tablets", 《 EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS》 * |
| 孙西洋: "盐酸***药物树脂液体缓释制剂研究", 《中国优秀博硕士学位论文全文数据库（硕士） 医药卫生科技辑》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115350152A (en) * | 2022-07-27 | 2022-11-18 | 武汉科福新药有限责任公司 | Propranolol sustained-release oral suspension and preparation method thereof |
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