CN103816113B - A kind of danshen-containing injections and preparation method thereof - Google Patents
A kind of danshen-containing injections and preparation method thereof Download PDFInfo
- Publication number
- CN103816113B CN103816113B CN201310436409.3A CN201310436409A CN103816113B CN 103816113 B CN103816113 B CN 103816113B CN 201310436409 A CN201310436409 A CN 201310436409A CN 103816113 B CN103816113 B CN 103816113B
- Authority
- CN
- China
- Prior art keywords
- danshen
- salviae miltiorrhizae
- radix salviae
- sodium
- injections
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of danshen-containing injections and preparation method thereof, danshen-containing injections of the present invention contains Radix Salviae Miltiorrhizae active component and buffering to agent combination, described Radix Salviae Miltiorrhizae active component comprise in danshensu sodium, protocatechualdehyde, rosmarinic acid and salvianolic acid B one or more; Described buffering comprises one or more of pharmaceutically acceptable antioxidant, organic monoacid and organic monoacid conjugate base to reagent, described antioxidant be selected from sodium pyrosulfite, sodium sulfite and sodium sulfite one or more.The invention also discloses the preparation method of described danshen-containing injections.Danshen-containing injections of the present invention has excellent quality stability, and preparation method is easy and simple to handle, without the need to special installation, be easily applied to suitability for industrialized production.
Description
Technical field: the present invention relates to field of pharmaceutical preparations, is specifically related to a kind of injection containing effective component in red sage and preparation method thereof.
Background technology:
Salviamiltiorrhizabung is the dry root and rhizome of Lamiaceae Salvia platymiscium Radix Salviae Miltiorrhizae (SalviamiltiorrhizaBunge), has effect of promoting blood circulation to remove obstruction in the collateral, stasis-dispelling and pain-killing, nourishing blood to tranquillize the mind, the relieving restlessness that clears away heart-fire.Modern pharmacology and clinical research show: Radix Salviae Miltiorrhizae has obvious protective effect to ischemic myocardium and Reperfu-sion heart, can improve the dysbolismus caused by histiocyte ischemia, anoxia; And there is anti-ex vivo thrombosis, antiplatelet aggregation, minimizing platelet, promote the effects such as fibrinogen degradation.In addition, Radix Salviae Miltiorrhizae can to improve in kidney microcirculation and increase renal hemodynamic, has certain protection and repair to ischemia kidney, and the effect such as antiulcer, the reparation of antibacterial, antiinflammatory, adjustment tissue and regeneration.The active component of salviamiltiorrhizabung mainly contains fat-soluble and water solublity two class, and liposoluble constituent is TANSHINONES, cryptotanshinone, Tanshinone II etc. mainly; Water soluble ingredient is danshensu, protocatechualdehyde, rosmarinic acid, alkannic acid, caffeic acid, salvianolic acid (A, B, C, D, E, F, G) etc. mainly, and the composition that in red rooted salvia, content is the highest is salvianolic acid B.Salvianolic acid B is easily degraded in the solution, Major degradation pathways is Ester hydrolysis and benzofuran open loop, danshensu, protocatechualdehyde, caffeic acid, alkannic acid and salvianolic acid E are the main degradation products of salvianolic acid B, and wherein danshensu, alkannic acid are hydrolyzate, protocatechualdehyde is oxidation product, salvianolic acid E is benzofuran open-loop products.Because salvianolic acid constituents is unstable in aqueous, the salvianolic acid B class preparation of listing all makes freeze-dried powder, is also developing the freeze-dried powder of salvianolic acid A.And danshen-containing injections such as the main component in Radix Salviae Miltiorrhizae Injection, DANXIANG GUANXIN ZHUSHEYE, XIANGDAN ZHUSHEYE and salvianic acid A sodium injection is danshensu.
Components in danshen injection take Radix Salviae Miltiorrhizae as one of raw material, through the sterilization preparation that extracting and developing, the step such as refining are made.In Radix Salviae Miltiorrhizae, the extracting method of effective ingredient has decocting method, water extraction wine sinks method, infusion process, percolation, circumfluence method etc.In the industrial production, how first the red sage root water soluble ingredient of extraction to be made " Salvia miltiorrhiza Bge water extraction concentrated solution ", red sage root water soluble ingredient is danshensu and protocatechualdehyde mainly, then is mixed with the Radix Salviae Miltiorrhizae Injection of pharmaceutical preparation specification further or is re-dubbed the Radix Salviae Miltiorrhizae Injection of compound recipe with other Chinese medicine extraction liquid.Research shows, be mixed with in the production process of danshen-containing injections from Salvia miltiorrhiza Bge water extraction concentrated solution, and in the storage process of danshen-containing injections, also change in various degree can all be there is in the content of the Radix Salviae Miltiorrhizae active component in injection, also can make injection that muddiness etc. occurs, directly affect the product quality of injection.
Except preparing danshensu class injection with " Salvia miltiorrhiza Bge water extraction concentrated solution ", also danshensu class injection can be prepared, the same existence and stability problem of this danshensu class injection with one or more Radix Salviae Miltiorrhizae active component of higher degree.
Optimizing the preparation method of danshen-containing injections, improve danshen-containing injections stability and quality level, ensure the drug safety of patient and the curative effect of product, is the difficult problem that pharmacy industry urgently seeks to solve.
CN101897754A discloses a kind of Salvia miltiorrhiza composition injection containing polyethyleneglycol-12-hydroxy stearin, while acquisition maxima solubility, improve clarity of injection, solve Radix Salviae Miltiorrhizae Injection and easily occur problems such as precipitating, muddy in storage and autoclaving process.
CN101884667 discloses the red drug injection of a kind of perfume (or spice) containing polyethyleneglycol-12-hydroxy stearin, improve the clarity of fragrant red drug injection preparation, solve fragrant red drug injection preparation adopt existing cosolvent storage and autoclaving process in occur easily become sour, cause impurity content high, easily with ingredient generation chemical change, in storage process, there is the problems such as solution muddiness.
CN102342909A discloses a kind of preparation method of salvianic acid A sodium injection, it is characterized in that the stability received with danshensu in antioxidant protection injection.The content of this injection danshensu sodium is 5% ~ 200%, and antioxidant content is 5% ~ 10%.
Summary of the invention:
Technical problem to be solved by this invention is the performance in order to improve danshen-containing injections, with its drug effect of better performance, and provides a kind of and has danshen-containing injections of more excellent stability and preparation method thereof.
" Salvia miltiorrhiza Bge water extraction concentrated solution " and some method for makings of other compound recipe composition concentrated solutions are described below:
" Salvia miltiorrhiza Bge water extraction concentrated solution " method for making of Radix Salviae Miltiorrhizae Injection: get Radix Salviae Miltiorrhizae 1500g, decoct with water three times, 2 hours first times, second, three times each 1.5 hours, collecting decoction, filter, filtrate reduced in volume to relative density is 1.15 ~ 1.28(60 DEG C of survey) clear paste, adding ethanol makes alcohol content be 75%, cold preservation, it is 1.16 ~ 1.26(60 DEG C of survey that filtrate is concentrated into relative density) clear paste, adding ethanol makes alcohol content be 85%, alcohol deposit fluid sodium hydroxide solution adjust ph to 8 ~ 9, cold preservation, filtrate adjusts back pH if desired to neutral, and reclaim ethanol extremely without alcohol taste, injecting water to relative density is 1.01 ~ 1.05(60 DEG C of survey) clear paste.With hydrochloric acid solution adjust ph to 2 ~ 3, cold preservation, filter, filtrate is with sodium hydroxide solution adjust ph to 5.5 ~ 6.5, and being concentrated into relative density is 1.02 ~ 1.06(60 DEG C of survey) clear paste, cold preservation; Or cold preservation, filter, it is 1.02 ~ 1.06(60 DEG C of survey that filtrate is concentrated into relative density) clear paste, with hydrochloric acid solution adjust ph to 2 ~ 3, cold preservation.Filter, filtrate, with sodium hydroxide solution adjust ph to 6.8 ~ 7.0, adds appropriate water for injection, boils half an hour, be chilled to 80 DEG C, add proper amount of active carbon, filter, let cool rear cold preservation, filter, by hydrochloric acid solution adjust ph to about 6.5 ~ 7.2, i.e. obtained " Salvia miltiorrhiza Bge water extraction concentrated solution ".Then can be made into the Radix Salviae Miltiorrhizae Injection of 1000ml.
" Salvia miltiorrhiza Bge water extraction concentrated solution " method for making of DANXIANG GUANXIN ZHUSHEYE: get Radix Salviae Miltiorrhizae 1000g and Lignum Dalbergiae Odoriferae 100g.Lignum Dalbergiae Odoriferae adds water infiltration 2 hours, carries out vapor distillation, collects distillate and is about 700ml, cold preservation 24 hours, divide the layer that deoils, filter, and the another device of aqueous solution is collected, i.e. obtained Lignum Dalbergiae Odoriferae aqueous solution.Radix Salviae Miltiorrhizae decocts with water three times, each 2 hours, collecting decoction, filters, filtrate is concentrated into 500ml, adds ethanol and makes alcohol content reach 75%, cold preservation 48 hours, filter, filtrate recycling ethanol, is concentrated into about 200ml, adding ethanol again makes alcohol content reach 85%, cold preservation 48 hours, filters, filtrate recycling ethanol, is concentrated into 120ml, adds water for injection to 1000ml, cold preservation 16 hours, filter, filtrate is concentrated into about 250ml.Cold preservation 72 hours, with 10% sodium hydroxide solution adjust ph to 6.0 ~ 6.8, add active carbon by 0.1% ~ 0.4% of medical material amount, boil 30 minutes, filter, filtrate uses dilute hydrochloric acid adjust ph to 4 again, adds medicinal charcoal by 0.1% ~ 0.4% of medical material amount, boils 30 minutes, cold preservation more than 24 hours, filter, filtrate uses 10% sodium hydroxide solution adjust ph to 6.5 ~ 7.0 again, i.e. obtained " Salvia miltiorrhiza Bge water extraction concentrated solution ".Then can be made into the DANXIANG GUANXIN ZHUSHEYE of 1000ml.
" Salvia miltiorrhiza Bge water extraction concentrated solution " method for making of XIANGDAN ZHUSHEYE: get Radix Salviae Miltiorrhizae 1000g and Lignum Dalbergiae Odoriferae 1000g.Lignum Dalbergiae Odoriferae adds water infiltration, carries out vapor distillation, collects distillate and is about 500ml, cold preservation 24 hours, divide the layer that deoils, and the another device of aqueous solution is collected, i.e. obtained Lignum Dalbergiae Odoriferae aqueous solution.Radix Salviae Miltiorrhizae decocts with water three times, and first time adds 8 times of water gagings, decocts 2 hours, second, respectively add 6 times three times, 5 times of water gagings, each decoction 1.5 hours, collecting decoction, filter, filtrate is concentrated into 670 ~ 760ml, adding ethanol makes alcohol content reach 75%, leave standstill 40 hours, filter, filtrate recycling ethanol, be concentrated into about 330ml, adding ethanol again makes alcohol content reach 85%, leave standstill 40 hours, 1% active carbon is by volume added in solution, stir 1 hour, filter, filtrate recycling ethanol, be concentrated into 200 ~ 300ml, add water for injection 1000 ~ 1650ml, leave standstill 16 hours, filter, filtrate is concentrated into about 330ml, adding ethanol makes alcohol content reach 80%, leave standstill 24 hours, filter, filtrate is concentrated into about 330ml, inject water to about 500ml, with 10% sodium hydroxide solution adjust ph to 6.8 ~ 7.0, boil 1 hour, 1% active carbon is by volume added in solution, boil 15 minutes, filter, filtrate uses 10% sodium hydroxide solution adjust ph to about 6.8 again, inject water to about 500ml.I.e. obtained " Salvia miltiorrhiza Bge water extraction concentrated solution ".Then can be made into the XIANGDAN ZHUSHEYE of 1000ml.
The method for making of Salvia miltiorrhiza Bge water extraction concentrated solution is not limited to the extraction process of three above-mentioned conventional danshen-containing injections, changes extraction process or changes technological parameter, can obtain the water extraction concentrated solution containing various ratio and variable concentrations Radix Salviae Miltiorrhizae active component.Also can with chemosynthesis or from Radix Salviae Miltiorrhizae the active component of extraction purification for the preparation of danshensu class injection, as salvianic acid A sodium injection.
The present inventor, through further investigation, finds to add in the drug injection or oral liquid of some instability and specifically cushions reagent on a small quantity, can obtain the effect of beyond thought raising stability.Breakthrough is obtained equally in the research improving danshen-containing injections stability, add and specifically cushion reagent on a small quantity, the stability of danshen-containing injections can be significantly improved, greatly reduce Radix Salviae Miltiorrhizae Injection in preparation, fill, sterilizing and storage process each factor to the adverse effect of product stability.On the one hand, the pH value of injection is controlled in a suitable scope, make the main active in injection keep stable, prevent because in the injection caused by pH value fluctuation, each constituents changes; On the other hand, improve the oxidation resistance of injection, prevent the main active in injection to be oxidized, some materials in blocking-up injection are on the impact of active component.
The present invention is solved the problems of the technologies described above by following technical proposals:
The present invention relates to a kind of danshen-containing injections, it contains Radix Salviae Miltiorrhizae active component and pharmaceutically acceptable buffering to agent combination.Described Radix Salviae Miltiorrhizae active component comprise in danshensu sodium, protocatechualdehyde, rosmarinic acid and salvianolic acid B one or more; Described buffering comprises one or more of pharmaceutically acceptable antioxidant, organic monoacid and organic monoacid conjugate base to reagent, described antioxidant be selected from sodium pyrosulfite, sodium sulfite and sodium sulfite one or more.
Further, described Radix Salviae Miltiorrhizae active component is danshensu sodium, or mainly comprises danshensu sodium and protocatechualdehyde.Described Radix Salviae Miltiorrhizae active component can further include rosmarinic acid and salvianolic acid B, as comprised danshensu sodium, protocatechualdehyde rosmarinic acid and salvianolic acid B.
When in described danshen-containing injections, when described Radix Salviae Miltiorrhizae active component is only danshensu sodium, described antioxidant can be selected from sodium pyrosulfite, sodium sulfite, sodium sulfite, dibenzylatiooluene (BHT) or propyl gallate one or more.
The content of described Radix Salviae Miltiorrhizae active component is containing 0.5 ~ 40mg in every 1ml danshen-containing injections, is preferably containing 1.0 ~ 20mg in every 1ml danshen-containing injections.
Further, in described Radix Salviae Miltiorrhizae active component, the mass ratio of danshensu sodium, protocatechualdehyde, rosmarinic acid and salvianolic acid B is (2.3 ~ 15.1): (0.18 ~ 5.8): (0.08 ~ 5.5): (0.4 ~ 4.2).
Described Radix Salviae Miltiorrhizae active component can be obtained by the method for chemosynthesis; Or also can be obtained by Chinese medicine extraction purification; Or described Radix Salviae Miltiorrhizae active component is contained in the water extraction concentrated solution of Radix Salviae Miltiorrhizae.The water extraction concentrated solution of described Radix Salviae Miltiorrhizae can adopt conventional decoction and alcohol sedimentation technique preparation, also can adopt aqueous solution of alcohol or extract containing aqueous slkali.
Described buffering is made up of pharmaceutically acceptable antioxidant and organic monoacid agent combination, or be made up of pharmaceutically acceptable antioxidant and organic monoacid and organic monoacid conjugate base, or be made up of pharmaceutically acceptable organic monoacid and organic monoacid conjugate base.Organic monoacid be selected from citric acid, tartaric acid, malic acid and lactic acid one or more.Organic monoacid conjugate base be selected from sodium citrate, sodium tartrate, natrium malicum and sodium lactate one or more.
In described danshen-containing injections, the percentage ratio (g/100ml) that the quality sum of described sodium pyrosulfite, sodium sulfite and sodium sulfite accounts for injection volume is 0.03% ~ 0.5%, is preferably 0.03% ?0.25%, more preferably 0.05% ~ 0.2%.
Cushion the preferred sodium sulfite of agent combination and the combination of citric acid or the combination of sodium sulfite and citric acid; The mass ratio of sodium sulfite and citric acid monohydrate is 1:5 ~ 1:0.5, and preferred 1:4 ~ 1:0.5, is more preferably 1:3 ~ 1:1; The mass ratio of sodium sulfite and citric acid monohydrate is 1:8 ~ 1:0.5, is preferably 1:4 ~ 1:1.
When in described danshen-containing injections, when described Radix Salviae Miltiorrhizae active component is danshensu sodium, cushion the combination to one or more in the preferred sodium sulfite of agent combination, sodium sulfite, dibenzylatiooluene, propyl gallate, sodium citrate and citric acid.The combination of the combination of the combination of the combination of the combination of such as sodium sulfite and citric acid or sodium sulfite and citric acid or dibenzylatiooluene and citric acid or propyl gallate and citric acid and sodium citrate or citric acid and sodium citrate.Buffering is in agent combination, and the mass ratio of sodium sulfite and citric acid monohydrate can be 1:5 ~ 1:0.5, and preferred 1:4 ~ 1:0.5, is more preferably 1:3 ~ 1:1; The mass ratio of sodium sulfite and citric acid monohydrate can be 1:8 ~ 1:0.5, is preferably 1:4 ~ 1:1, more preferably 1:3 ~ 1:1; The mass ratio of citric acid monohydrate and sodium citrate dihydrate can be 1:9 ~ 1:0.1, is preferably 1:5 ~ 1:0.3; The mass ratio of dibenzylatiooluene and citric acid one water thing can be 1:5 ~ 1:0.5, preferred 1:4 ~ 1:1.6; The mass ratio of propyl gallate and citric acid one water thing can be 1:5 ~ 1:0.5, preferred 1:4 ~ 1:1.9; Aforementioned proportion can combine the selection of reagent according to buffering.
The percentage ratio (g/100ml) that buffering accounts for injection volume to the quality of reagent is 0.03% ~ 1.0%, and be preferably 0.1% ?0.8%, better is 0.1% ~ 0.5%.Buffering makes the pH of danshen-containing injections be 3.0 ~ 6.0 to agent combination, is preferably 3.5 ~ 5.0.
Also can add other antioxidant in danshen-containing injections, other described antioxidant be selected from thiourea, sodium thiosulfate, L ?one or more in cysteine, sodium ascorbate, butylated hydroxyarisol, dibenzylatiooluene, tertiarybutylhydroquinone, ascorbyl palmitate and propyl gallate.The percentage ratio (g/100ml) that the quality of other antioxidant described accounts for injection volume is 0.03% ~ 0.5%, is preferably 0.05% ~ 0.2%.
Obvious, except the above-mentioned buffering enumerated is to reagent, as required, the pharmaceutical field acceptable adjuvant of danshen-containing injections of the present invention also selectively containing other kinds, as solubilizing agent, stabilizing agent and excipient.Equally, as required, except Radix Salviae Miltiorrhizae Injection, danshen-containing injections of the present invention also can contain other active component, as Chinese medicine extract such as Lignum Dalbergiae Odoriferae extract, Flos Carthami extract, Radix Astragali extract, Radix Angelicae Sinensis extracts, the ingredients such as example hydrochloric acid ligustrazine, with obtained compound preparation.As embodiment is specifically enumerated, can contain the distillate of Lignum Dalbergiae Odoriferae, the distillate of described Lignum Dalbergiae Odoriferae can adopt conventional steam distillation preparation.Lignum Dalbergiae Odoriferae can be added the laggard row steam distillation of water infiltration by described steam distillation, divides the layer that deoils to obtain after cold preservation.During steam distillation, every 100g Lignum Dalbergiae Odoriferae prepares 49-700ml Lignum Dalbergiae Odoriferae distillate.Preferably, every 1000ml danshen-containing injections raw material can contain the distillate 480-700ml of described Lignum Dalbergiae Odoriferae.
By " Salvia miltiorrhiza Bge water extraction concentrated solution " and other compound recipe composition concentrated solutions, or the active component of Radix Salviae Miltiorrhizae is made danshen-containing injections and is comprised the steps:
(1) selected buffering is dissolved agent combination; Dissolving solvent for use is water for injection.
(2) Radix Salviae Miltiorrhizae active component and water for injection are uniformly mixed.As adopted chemosynthesis or the active component preparation of extraction purification from Radix Salviae Miltiorrhizae, then appropriate water for injection can be added in proportion container, then add recipe quantity chemosynthesis or from Radix Salviae Miltiorrhizae the active component of extraction purification, be uniformly mixed; As adopted Salvia miltiorrhiza Bge water to extract concentrated solution preparation, then Salvia miltiorrhiza Bge water can be extracted concentrated solution and join in proportion container, add appropriate water for injection, be uniformly mixed.As also contained other active component in injection, can add in the lump in this step.
(3) by solution mix homogeneously prepared by (1), (2), be supplemented to full dose with water for injection, continue to be mixed to evenly;
(4) filter: with the filter in suitable aperture, or degerming microfilter filters;
(5) embedding: filtrate is filled in packing container, or be filled in packing container after filling nitrogen, then seal;
(6) sterilizing: aseptic filtration, or moist heat sterilization, or the flowing steam after aseptic filtration supplements sterilizing;
(7) check, pack.
By method of the present invention, condition, and in conjunction with technology of preparing well known in the art, the various danshen-containing injections of excellent in stability can be obtained.
In the present invention, above-mentioned each optimum condition can on the basis meeting this area general knowledge combination in any, the preferred embodiments of the invention.
The present invention is raw materials used can be prepared voluntarily or commercially availablely to obtain, and adjuvant commercially.
Positive progressive effect of the present invention is:
(1) danshen-containing injections of the present invention has excellent quality stability.(2) danshen-containing injections of the present invention obviously can reduce the acid-base value fluctuation of danshen-containing injections.(3) preparation method of the present invention is easy and simple to handle, cost is low, without the need to special installation, is easily applied to suitability for industrialized production.
Detailed description of the invention:
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
Comparative example 1 and embodiment 1 Radix Salviae Miltiorrhizae Injection (being equivalent to red rooted salvia 1.5g/ml)
Embodiment 2 and embodiment 3 Radix Salviae Miltiorrhizae Injection (being equivalent to red rooted salvia 1.5g/ml)
Embodiment 4 Radix Salviae Miltiorrhizae Injection (being equivalent to red rooted salvia 1.5g/ml)
Comparative example 2 and embodiment 5 DANXIANG GUANXIN ZHUSHEYE (being equivalent to red rooted salvia 1.0g/ml, Lignum Dalbergiae Odoriferae medical material 0.1g/ml)
Embodiment 6 DANXIANG GUANXIN ZHUSHEYE (being equivalent to red rooted salvia 1.0g/ml, Lignum Dalbergiae Odoriferae medical material 0.1g/ml)
Embodiment 7 and embodiment 8 DANXIANG GUANXIN ZHUSHEYE (being equivalent to red rooted salvia 1.0g/ml, Lignum Dalbergiae Odoriferae medical material 0.1g/ml)
Embodiment 9 XIANGDAN ZHUSHEYE (being equivalent to red rooted salvia 1.0g/ml, Lignum Dalbergiae Odoriferae medical material 1.0g/ml)
Embodiment 10 and embodiment 11 XIANGDAN ZHUSHEYE (being equivalent to red rooted salvia 1.0g/ml, Lignum Dalbergiae Odoriferae medical material 1.0g/ml)
Embodiment 12 salvianic acid A sodium injection (10mg/ml)
Embodiment 13 and embodiment 14 salvianic acid A sodium injection (20mg/ml)
Embodiment 15 salvianic acid A sodium injection (5mg/ml) and embodiment 16 salvianic acid A sodium injection (20mg/ml)
Embodiment 17 salvianic acid A sodium injection (10mg/ml)
Effect example 1 cushions reagent proportioning test
1, Radix Salviae Miltiorrhizae Injection sample preparation
2, Radix Salviae Miltiorrhizae Injection sample stability experiment
1) content assaying method
Chromatographic condition and system suitability take octadecylsilane chemically bonded silica as filler; Take acetonitrile as mobile phase A, with 0.05% trifluoroacetic acid aqueous solution for Mobile phase B, the regulation according to the form below carries out gradient elution; Flow velocity is 0.8ml per minute; Column temperature is 40 DEG C; Determined wavelength is 288nm.Number of theoretical plate calculates should be not less than 200000 by salvianolic acid B peak.
It is appropriate that danshensu sodium reference substance, protocatechualdehyde reference substance, rosmarinic acid reference substance and salvianolic acid B reference substance are got in the preparation of reference substance solution, accurately weighed, 10% methanol solution adding 0.2% glacial acetic acid makes the mixed solution of every 1ml containing danshensu sodium 0.20mg, protocatechualdehyde 50 μ g, rosmarinic acid 50 μ g and salvianolic acid B 50 μ g, to obtain final product.
The preparation precision of need testing solution measures this product 2ml, puts in 10ml measuring bottle, and 10% methanol solution adding 0.2% glacial acetic acid is diluted to scale, shakes up, to obtain final product.
Algoscopy is accurate respectively draws reference substance solution and each 5 μ l of need testing solution, injection liquid chromatography, measures, to obtain final product.
2) sample acceleration environment: sample is placed in constant humidity cabinet, sets 60 DEG C ± 2 DEG C, carries out acceleration test in 5 days.
3) stability data compares
As can be seen from the above data, compared with comparative example, technical scheme colour stability of the present invention is better, and pH value is more stable, and effective ingredient before acceleration after change also reduce.
Effect example 2 sample solution pH value and color comparative experiments
1) content assaying method is with effect example 1.
2) sample acceleration environment: sample is placed in constant humidity cabinet, sets 60 DEG C ± 2 DEG C, carries out acceleration test in 5 days.
3) stability data compares
The comparative experiments of effect example 3 sample stability
1) content assaying method is with effect example 1.
2) sample acceleration environment: sample is placed in climatic chamber, sets 40 DEG C ± 2 DEG C, RH75% ± 5% condition, carries out test in 3 months.
3) stability data compares
As can be seen from the above data, compared with comparative example, technical scheme colour stability of the present invention is better, and pH value is more stable, and effective ingredient before acceleration after change also reduce.
Claims (9)
1. a danshen-containing injections, it is characterized in that containing Radix Salviae Miltiorrhizae active component and cushion agent combination, described Radix Salviae Miltiorrhizae active component is danshensu sodium or is made up of danshensu sodium, protocatechualdehyde, rosmarinic acid and salvianolic acid B, and the mass ratio of danshensu sodium, protocatechualdehyde, rosmarinic acid and salvianolic acid B is (2.3 ~ 15.1): (0.18 ~ 5.8): (0.08 ~ 5.5): (0.4 ~ 4.2); Containing 0.5 ~ 40mg components in danshen active component in every 1ml danshen-containing injections; The percentage ratio (g/100ml) that the quality of described buffering to reagent accounts for injection volume is 0.03% ~ 1.0%; Described buffering is selected from the combination of sodium sulfite and citric acid or the combination of sodium sulfite and citric acid to agent combination; The mass ratio of sodium sulfite and citric acid monohydrate is 1:5 ~ 1:0.5; The mass ratio of sodium sulfite and citric acid monohydrate is 1:8 ~ 1:0.5.
2. danshen-containing injections as claimed in claim 1, is characterized in that the content of described Radix Salviae Miltiorrhizae active component is containing 1.0 ~ 20mg in every 1ml danshen-containing injections.
3. danshen-containing injections as claimed in claim 1, is characterized in that described Radix Salviae Miltiorrhizae active component comprises the Radix Salviae Miltiorrhizae active component obtained by chemosynthesis or Chinese medicine extraction purification, or is contained in the Radix Salviae Miltiorrhizae active component in Salvia miltiorrhiza Bge water extraction concentrated solution after Chinese medicine extraction.
4. danshen-containing injections as claimed in claim 1, described in is characterized in that; The mass ratio of sodium sulfite and citric acid monohydrate is 1:3 ~ 1:1, and the mass ratio of sodium sulfite and citric acid monohydrate is 1:4 ~ 1:1.
5. danshen-containing injections as claimed in claim 1, is characterized in that described buffering makes the pH of danshen-containing injections be 3.0 ~ 6.0 to agent combination.
6. danshen-containing injections as claimed in claim 1, is characterized in that the percentage ratio (g/100ml) that the quality of described buffering to reagent accounts for injection volume is 0.1% ~ 0.5%.
7. as claim 1 ?6 arbitrary as described in danshen-containing injections, it is characterized in that also can adding other antioxidant in danshen-containing injections, other described antioxidant be selected from thiourea, sodium thiosulfate, L ?one or more in cysteine, sodium ascorbate, butylated hydroxyarisol, dibenzylatiooluene, tertiarybutylhydroquinone, ascorbyl palmitate and propyl gallate.
8. danshen-containing injections as claimed in claim 7, is characterized in that, the percentage ratio (g/100ml) that the quality of other antioxidant described accounts for injection volume is 0.03% ~ 0.5%.
9. as claim 1 ?the preparation method of danshen-containing injections as described in 8 arbitrary claim, it is characterized in that, comprise the following steps: described buffering to dissolve agent combination, add the Radix Salviae Miltiorrhizae active component of dissolving, mix homogeneously, benefit adds to the full amount of water for injection, and continues mix homogeneously; With the plate filter in suitable aperture, or degerming microfilter filters; Filtrate is filled in container, or is filled in container after filling nitrogen; Sterilizing, or sterilizing is supplemented after aseptic filtration; Inspection, packaging.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310436409.3A CN103816113B (en) | 2012-11-19 | 2013-09-23 | A kind of danshen-containing injections and preparation method thereof |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2012104678857 | 2012-11-19 | ||
| CN201210467885.7 | 2012-11-19 | ||
| CN201210467885 | 2012-11-19 | ||
| CN201310436409.3A CN103816113B (en) | 2012-11-19 | 2013-09-23 | A kind of danshen-containing injections and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103816113A CN103816113A (en) | 2014-05-28 |
| CN103816113B true CN103816113B (en) | 2016-04-27 |
Family
ID=50751602
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310436409.3A Active CN103816113B (en) | 2012-11-19 | 2013-09-23 | A kind of danshen-containing injections and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103816113B (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450051A (en) * | 2007-12-07 | 2009-06-10 | 苑立超 | Monomer salvianolic acid B injection and preparation method thereof |
| CN101596182A (en) * | 2008-06-05 | 2009-12-09 | 山东靶点药物研究有限公司 | Contain pharmaceutical composition, its preparation method, the purposes of salviol acid A and contain the lyophilized injectable powder and the aqueous injection of said composition |
| CN102342909A (en) * | 2010-07-30 | 2012-02-08 | 湖南康普医药研究院 | Preparation method of salvianic acid A sodium injection |
-
2013
- 2013-09-23 CN CN201310436409.3A patent/CN103816113B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101450051A (en) * | 2007-12-07 | 2009-06-10 | 苑立超 | Monomer salvianolic acid B injection and preparation method thereof |
| CN101596182A (en) * | 2008-06-05 | 2009-12-09 | 山东靶点药物研究有限公司 | Contain pharmaceutical composition, its preparation method, the purposes of salviol acid A and contain the lyophilized injectable powder and the aqueous injection of said composition |
| CN102342909A (en) * | 2010-07-30 | 2012-02-08 | 湖南康普医药研究院 | Preparation method of salvianic acid A sodium injection |
Non-Patent Citations (2)
| Title |
|---|
| HPLC法测定丹参类注射液中4种水溶性成分含量;潘英妮 等;《沈阳药科大学学报》;20040531;第21卷(第3期);第196-200页 * |
| 添加剂对丹参酚酸B水溶液稳定性的影响;曲桂武 等;《中草药》;20051130;第36卷(第11期);第1654-1655页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103816113A (en) | 2014-05-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| RU2716218C2 (en) | Composition for injection based on a fat emulsion of cabazitaxel, a method for its preparation and application | |
| CN105031207A (en) | Sugar-free pulse-activating decoction oral liquid and preparation method thereof | |
| Dai et al. | Honey in traditional Chinese medicine: A guide to future applications of NADES to medicines | |
| CN103816113B (en) | A kind of danshen-containing injections and preparation method thereof | |
| TWI684451B (en) | Silybin injection and its preparation method | |
| CN1273828C (en) | Capsule for treating cold and cough, its preparation and detection method | |
| CN101708156A (en) | Camptothecin medicament injection solution and injection and preparation method thereof | |
| CN102178236A (en) | Blood sugar reducing and cardiovascular and cerebrovascular complication preventing soft capsules and preparation method thereof | |
| CN101455648B (en) | Puerarin freeze-drying preparation | |
| CN103977336A (en) | Pharmaceutical composition with myocardial ischemia resisting effect and preparation method and application thereof | |
| CN104367633A (en) | Medicine combination with antibacterial and synergically-antibacterial effects, and preparation method and application | |
| KR20100130020A (en) | A composition comprising novel black ginseng without tumor promoting agents such as benzopyran and the extract thereof obtained by novel process | |
| CN110227062B (en) | Baicalin liposome ointment and preparation method thereof | |
| CN105125482B (en) | Puerarin injection and quality control method | |
| CN103520186B (en) | Pharmaceutical composition of a kind of fat-soluble vitamin for injection and preparation method thereof | |
| CN105147724B (en) | A kind of Mannitol sodium chloride injection and preparation method thereof | |
| CN105147664B (en) | Puerarin injection and preparation method | |
| CN102247329B (en) | 5,6,7,4'-tetrahydroxyflavone powder injection and preparation method thereof | |
| CN101507747A (en) | Preparation method of astragalus total-saponin sodium chloride injector | |
| CN102579574B (en) | Method for preparing compound red-rooted salvia root oral liquid | |
| CN114767760B (en) | A composition with liver protecting effect | |
| CN105031375A (en) | Medicine for treating cow mastitis and preparation method, detecting method and application of medicine | |
| CN100349582C (en) | Oil seed bruceae lyophilized powder for injection and its preparing method | |
| CN1961911A (en) | Lyophilized powder injection containing red sage root and dalbergia wood volatile oil and preparation method thereof | |
| CN105055324A (en) | Platinum anticancer oxaliplatin composition |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee | ||
| CP01 | Change in the name or title of a patent holder |
Address after: 201806, Shanghai, Jiading District outer Pine Road No. 446 Patentee after: Shanghai Chinese Medicine Pharmaceutical Co. Ltd. Address before: 201806, Shanghai, Jiading District outer Pine Road No. 446 Patentee before: Shanghai Zhongxi Pharmaceutical Co., Ltd. |