CN101057841A - 'Yanhuning' frozen-dried powder injection and its preparation method - Google Patents
'Yanhuning' frozen-dried powder injection and its preparation method Download PDFInfo
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Abstract
The invention discloses a freeze dried injection of potassium sodium dehydroandrographolide succinate which is prepared from potassium sodium dehydroandrographolide succinate, ionic cushion pairs and anti-oxidizing agents, the preferred ionic cushion pairs being phosphate cushion pairs, and the antioxidant can be L-cysteine hydrochloride.
Description
Technical field
The present invention relates to a kind of medicament and preparation method thereof, specifically 'Yanhuning ' frozen-dried powder injection and preparation method thereof.
Background technology
Andrographolide, chemical name is: 14-deshydroxy-11,12-two dehydrogenation andrographolide-3,19-disuccinic acid half ester k-na salt, molecular formula: C28H34KNaO10H2O; Molecular weight: 610.68.It can suppress early stage capillary permeability and increases and inflammatory exudation and edema, can excited specifically hypophysis-adrenal cortex function, and promote ACTH to discharge, increase the biosynthesis of ACTH in the antepituitary; External effect with multiple viruses such as deactivation adenovirus, influenza virus, Respiroviruses.Zoopery have anti-early, in pregnant effect.Heat-clearing and toxic substances removing and antivirus action are arranged, be mainly used in viral pneumonia and viral upper respiratory tract infection.
Existing injection andrographolide is the aseptic freeze-dried product of andrographolide, can add an amount of aseptic injection and make diluent with sodium chloride.It is pressed holding conditions (airtight, at shady and cool dry place) preserve, because of its pH environment instability, so that content descends is very fast, content is promptly reduced to lower limit after have 1 year, can't reach 2 years effect phases.
Summary of the invention
The objective of the invention is to provides a kind of chemically stable, effect duration long 'Yanhuning ' frozen-dried powder injection at above-mentioned deficiency; Another object of the present invention is to provide the preparation method of described injectable powder.
The main cause of injection andrographolide inefficacy is hydrolysis and Oxidation, so the stability key that needs to improve the injection andrographolide is the pH value of control solution and adds suitable antioxidant.
Therefore, the present invention uses andrographolide, ion buffering to be prepared into lyophilized injectable powder to reaching antioxidant as primary raw material.Described ion buffering to be phosphate-buffered to, carbonate buffering to or amino acid salts cushion rightly, it is right to be preferably phosphate-buffered.Described antioxidant is L-cysteine hydrochloride, L-cysteine or sodium sulfite, is preferably the L-cysteine hydrochloride.
Further, the present invention has established an optimization formula, and it comprises the primary raw material of following weight ratio: andrographolide 720～880, sodium hydrogen phosphate 80.64～98.56, sodium dihydrogen phosphate 58.05～70.95, L-cysteine hydrochloride 4.41～8.36.More preferably, andrographolide 800, sodium hydrogen phosphate 89.6, sodium dihydrogen phosphate 64.5, L-cysteine hydrochloride 4.9～7.6.
The present invention also provides the method for preparing above-mentioned injectable powder, it is characterized in that the method comprising the steps of: get andrographolide and regulate pH to 6.0～7.0 with the water for injection dissolving, add the ion buffering to aqueous solution and antioxidant aqueous solution, stirring evenly the back handles with activated carbon adsorption, regulate pH to 6.3～7.1, benefit adds to the full amount of water for injection, and stirs the back lyophilizing promptly.
More particularly, the method comprising the steps of: 45 ℃～60 ℃ the water for injection of measuring amount of preparation 70%, the andrographolide that adds recipe quantity while stirring, keep 45 ℃～60 ℃ of temperature, after treating all dissolvings, be cooled to room temperature immediately, with 10% sodium bicarbonate solution adjust pH to 6.0～7.0, add the ion buffering to aqueous solution, stir evenly the active carbon that the back adds percentage by weight 0.2～1.0%, stirring and adsorbing 20 minutes, carbon removal, with 10% sodium bicarbonate solution adjust pH to 6.3～7.1, benefit adds to the full amount of water for injection, and stirs the back lyophilizing promptly.
Preferably, the method comprising the steps of: 50 ℃～55 ℃ the water for injection of measuring amount of preparation 70%, the andrographolide that adds recipe quantity while stirring, keep 50 ℃～55 ℃ of temperature, after treating all dissolvings, be cooled to room temperature immediately, with 10% sodium bicarbonate solution adjust pH to 6.6～6.8, add the ion buffering to aqueous solution and antioxidant aqueous solution, stir evenly the active carbon that the back adds percentage by weight 0.4～0.7%, stirring and adsorbing 20 minutes, carbon removal, to preferred 6.7～6.9, benefit adds to the full amount of water for injection, and stirs with 10% sodium bicarbonate solution adjust pH.Be cooled to fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing.
Preparation method of the present invention is at the omnidistance nitrogen filled protection of process for preparation, to prevent the oxidation of andrographolide to greatest extent.
Full dose of the present invention is meant that the w/v 1: 14～21 according to prescription total amount and water for injection adds water for injection.
Lyophilized injectable powder of the present invention since added ion buffering to and antioxidant, make its pH ambient stable, oxidation rate is slow, has improved its storage life effectively.
Description of drawings
Fig. 1 is a vascular stimulation administration group experimental result;
Fig. 2 is a vascular stimulation matched group experimental result;
Fig. 3 is a muscular irritation administration group experimental result;
Fig. 4 is a muscular irritation matched group experimental result.
The specific embodiment
Following embodiment is used to further specify the present invention, but is not used for limiting the scope of the invention.
The preparation of embodiment 1 'Yanhuning ' frozen-dried powder injection
Get andrographolide 800g, remain on 50 ℃～55 ℃ dissolvings, adjust pH to 6.7 with the water for injection of 55 ℃ of 14000ml; Get sodium hydrogen phosphate 89.6g and sodium dihydrogen phosphate 64.5g respectively, with the water for injection dissolving of 1000ml; Get L-cysteine hydrochloride 6g, with the dissolving of 1000ml water for injection, with above-mentioned three kinds of solution mix homogeneously, activated carbon adsorption, pH value to 6.8 is regulated in carbon removal, add water for injection to 20000ml, stir, fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing gets product.
The preparation of embodiment 2 'Yanhuning ' frozen-dried powder injections
Get andrographolide 720g, with the water for injection dissolving of 50 ℃ of 12000ml, adjust pH to 6.0; Get sodium hydrogen phosphate 80.64g and sodium dihydrogen phosphate 50.05g respectively, dissolve with water for injection; Get L-cysteine hydrochloride 4.9g, with the water for injection dissolving, with above-mentioned three kinds of solution mix homogeneously, add activated carbon adsorption, carbon removal, adjusting pH value to 6.3 by weight 0.4%, add water for injection to 13000ml, stir, fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing gets product.
The preparation of embodiment 3 'Yanhuning ' frozen-dried powder injections
Get andrographolide 880g, with the water for injection dissolving of 60 ℃ of 13000ml, adjust pH to 7.0; Get sodium hydrogen phosphate 98.56g and sodium dihydrogen phosphate 70.95g respectively, with water for injection 1000ml dissolving; Get L-cysteine hydrochloride 7.6g, with water for injection 1000ml dissolving, with above-mentioned three kinds of solution mix homogeneously, add activated carbon adsorption 20 minutes, carbon removal, adjusting pH value to 6.9 by weight 0.7%, add water for injection to 25000ml, stir, fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing gets product.
The preparation of embodiment 4 'Yanhuning ' frozen-dried powder injections
Get andrographolide 850g, with the water for injection dissolving of 53 ℃ of 12000ml, adjust pH to 6.6; Get sodium hydrogen phosphate 80g and sodium dihydrogen phosphate 60g respectively, dissolve with water for injection; Get L-cysteine hydrochloride 4.41g, with the water for injection dissolving, with above-mentioned three kinds of solution mix homogeneously, add activated carbon adsorption 20 minutes, carbon removal, adjusting pH value to 7.1 by weight 0.2%, add water for injection to 22000ml, stir, fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing gets product.
The preparation of embodiment 5 'Yanhuning ' frozen-dried powder injections
Get andrographolide 750g, with the water for injection dissolving of 45 ℃ of 10000ml, with 10% sodium bicarbonate solution adjust pH to 6.8; Get sodium hydrogen phosphate 90g and sodium dihydrogen phosphate 65g respectively, dissolve with water for injection; Get L-cysteine hydrochloride 8.36g, with the water for injection dissolving, with above-mentioned three kinds of solution mix homogeneously, by weight 1.0% adding activated carbon adsorption, carbon removal is regulated pH value to 6.7 with 10% sodium bicarbonate solution, add water for injection to 20000ml, stir, fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing gets product.
The research of embodiment 6 injection safety testings
(1) sensitivity test
Get 18 of Cavia porcelluss, male and female half and half, body weight 250～300g is divided into negative control group (5% glucose injection), positive controls (5% ovalbumin normal saline solution) and injection andrographolide at random and is tried thing group (being made into 1.6mg/ml with 5% glucose injection), 6 every group.The corresponding medicinal liquid 0.5ml/ of each treated animal every other day lumbar injection, totally three times.After first administration 14 days respectively, 21 days, get three at random for every group, the corresponding medicinal liquid 1ml/ of intravenous injection only, observe immediately after the administration that animal has or not sneeze, scratches nose, dry cough or cough, tremble, the anaphylaxis of perpendicular hair, tic, dyspnea, gatism, shock and death, be 15 minutes observing time.The anaphylaxis classification sees Table 1.
Table 1 anaphylaxis classification and decision method as a result
| The reaction classification | The reflection symptom | The result judges |
| 0 | No significant reaction | All there is not significant reaction as twice Cavia porcellus, think that to be subjected to the reagent hypersensitive test qualified, reflection progression reaches when (comprising 2 grades) more than 2 grades, thinks that to be subjected to the anaphylaxis of reagent thing defective. |
| 1 | Have and slightly grab nose, tremble or erect hair | |
| 2 | Cough is arranged several times, grab that nose trembles or perpendicular hair | |
| 3 | Repeatedly or continuously cough, with dyspnea or spasm, tic | |
| 4 | Spasm, tic, gatism, shock, death |
The Cavia porcellus anaphylaxis progression of the negative matched group of result is 0, does not have irritated reaction; The positive controls Cavia porcellus sneeze occurs, scratches nose, retch or cough, twitch, tremble, anaphylaxiss such as dyspnea, gatism, shock, and all dead in 15min, anaphylaxis progression is level Four, experimental condition is set up.6 Cavia porcelluss of injection andrographolide group all do not have irritated reaction, and anaphylaxis progression is 0.The injection andrographolide does not have sensitization to Cavia porcellus.The results are shown in Table 2.
Table 2 injection andrographolide hypersensitive test result
| Grouping | Number of animals | The sensitization natural law | Anaphylaxis progression | Have or not allergy | ||
| First | Second | The 3rd | ||||
| The injection andrographolide | 3 3 | 14 21 | 0 0 | 0 0 | 0 0 | (-) (-) |
| 5% glucose injection | 3 3 | 14 21 | 0 0 | 0 0 | 0 0 | (-) (-) |
| 5% ovalbumin | 3 3 | 14 21 | 4 4 | 4 4 | 4 4 | (+) (+) |
(-) do not have irritated reaction (+) anaphylaxis arranged
(2) hemolytic test
Get rabbit cardiac puncture blood sampling 10ml, with glass bead stir defibrinate after, with normal saline washing back centrifugal (3000rpm), remove supernatant, again with the normal saline cyclic washing for several times (all centrifugal supernatant of abandoning) until the supernatant redfree, it is standby to be made into 2% red blood cell suspension with normal saline by volume then.
Getting 7 in test tube, add the reagent liquid of different volumes and the red blood cell suspension of equal volume respectively by each pipe shown in the table 3, wherein the 6th manage not dosing, is 0.9% sodium chloride solution blank, and the 7th pipe adding distil water is done complete haemolysis contrast (positive control pipe).After each pipe shakes up gently, put in 37 ℃ of water-baths temperature and incubated 4 hours, observe whether each pipe has haemolysis and erythrocyte aggregation phenomenon in 0.25 hour to 4.0 hours, press the judgement of table 4 standard.The results are shown in Table 5.
The external hemolytic test application of sample of table 3 table
| Application of sample volume (ml) | Test tube number | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| 2% red blood cell suspension | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 | 2.5 |
| 0.9% sodium chloride solution | 2.0 | 2.1 | 2.2 | 2.3 | 2.4 | 2.5 | 0 |
| Distilled water | 0 | 0 | 0 | 0 | 0 | 0 | 2.5 |
| The injection andrographolide | 0.5 | 0.4 | 0.3 | 0.2 | 0.1 | 0 | 0 |
Table 4 haemolysis result judges
| Degree | Sign | Phenomenon |
| No haemolysis | - | Erythrocyte all sinks, upper strata liquid water white transparency |
| Part haemolysis | ± | Clear and bright redness of solution or brownish red,, there is a small amount of erythrocyte at the pipe end |
| Full haemolysis | + | The clear and bright redness of solution, the pipe end, is acellular residual |
| Coagulation | The erythrocyte aggregation in bulk does not disperse after shaking up |
External haemolysis of table 5 injection andrographolide and cell agglutination result of the test
| Time (hour) | Test tube number | ||||||
| 1 | 2 | 3 | 4 | 5 | 6 | 7 | |
| 0.25 | - | - | - | - | - | - | + |
| 0.5 | - | - | - | - | - | - | + |
| 0.75 | - | - | - | - | - | - | + |
| 1.0 | - | - | - | - | - | - | + |
| 2.0 | - | - | - | - | - | - | + |
| 3.0 | - | - | - | - | - | - | + |
| 4.0 | - | - | - | - | - | - | + |
Experimental result shows, injection andrographolide (being made into 1.6mg/ml with 5% glucose injection) group and 0.9% each pipe of sodium chloride solution group did not all have haemolysis in 0.25～4.0 hour, also do not have agglutination, the distilled water group produces red clear solution in each time point complete hemolysis.
(3) vascular stimulation test
Get 3 of 2.5～3.0kg rabbit, the male and female dual-purpose, adopt the ear contrast of the consubstantiality left and right sides, left side ear (is made into 1.6mg/ml with 5% glucose injection by the slow injection injection of auricular vein with andrographolide, the administration capacity is 5.0ml/), auris dextra waits the glucose injection of capacity to do contrast, every day 1 time, continuous 3 days.Whether perusal every day two groups of families rabbit ear injection site and peripheral vessels have edema, hyperemia etc. to stimulate phenomenon, and carry out the perusal scoring by the standard of table 6.After the last injection, put to death animal, respectively clip injection site auricular vein and the about 2cm of surrounding tissue, after 10% formaldehyde fixed, paraffin section, HE dyeing, situations such as microscopically observes that its inflammatory cell infiltration, blood vessel surrounding tissue are hemorrhage, thrombosis and necrosis.
Table 6 blood vessel irritation perusal standards of grading
| Observation index | Project | Scoring | The result judges (in overall score) |
| The congestion of blood vessel | Normally | 0 | |
| Congested | 1 | ||
| The blood vessel lines is unclear | 2 | ||
| Blood vessel becomes aubergine | 3 |
| The surrounding tissue edema | No edema | 0 | The heavy zest in≤4.5 moderate stimulations≤6.0 |
| Slight edema | 1 | ||
| Obvious edema | 2 | ||
| Serious edema | 3 |
Injection andrographolide successive administration is 3 days as a result, and perusal man rabbit ear vein blood vessel and surrounding tissue are not seen obvious redness, congested abnormal phenomena.Judge nonirritant by standards of grading, the results are shown in Table 7.As seen microscopically is observed: place, left ear injection andrographolide injection site blood vessel endothelium is continuous, complete, do not see hypertrophy, swelling, and the blood vessel surrounding tissue is not seen obvious inflammatory cell infiltration and necrosis, no thrombosis formation (as shown in Figure 1) in the tube chamber; Auris dextra (5% glucose injection) injection site vascular endothelial cell, lumen of vessels and surrounding tissue show no obvious abnormalities (as shown in Figure 2).Judge that by standards of grading the injection andrographolide does not have obvious blood vessel irritation.
Table 7 injection andrographolide blood vessel irritation perusal scoring
| Group | Dosage | Number of animals | Scoring |
| 5% glucose injection | 5.0ml/ only | 3 | 0 |
| The injection andrographolide | 5.0ml/ only | 3 | 0 |
(4) muscle irritation test
Get 3 of healthy rabbits, body weight is between 2.5-3.0kg, male, inject injection andrographolide (being made into 1.6mg/ml) 1ml with asepsis injector in each rabbit left side quadriceps femoris with 5% glucose injection, glucose injection 1ml is injected in contrast in the right side, 48h injection site muscle has or not phenomenons such as hyperemia, redness, degeneration, necrosis occur after observing injection then, and by muscular irritation reaction grade scale (seeing Table 8) marking and evaluation result.After the perusal, put to death animal, get injection site muscle 2cm
3, formaldehyde fixed is carried out histopathologic examination.
Table 8 muscular irritation reaction grade scale
| Irritant reaction | Order of reaction |
| No significant change | 0 |
| The mild hyperaemia scope is below 0.5 * 1cm | 1 |
| The congested scope of moderate is more than 0.5 * 1cm | 2 |
| Severe hyperemia is with myodegeneration | 3 |
| Necrosis occurs, the brown degeneration is arranged | 4 |
| The popularity necrosis | 5 |
As a result, by naked eyes and histological examination, the injection andrographolide to rabbit quadriceps femoris drug administration by injection after, produce phenomenons such as hyperemia, redness, degeneration, necrosis, the results are shown in Table 9.As seen microscopically is observed: injection andrographolide group and glucose injection group injection site muscular tissue there is no swelling, hypertrophy, and cellular morphology is intact, does not see inflammatory cell infiltration and necrosis, (shown in Fig. 3,4).Show that the injection andrographolide does not have muscle irritation.
Table 9 injection andrographolide muscular irritation macroscopic score
| The position | Observing time | No significant reaction | Mild reaction | The moderate reaction | The severe reaction | Degeneration necrosis | Serious downright bad | Average mark |
| Left side lower limb | 24h | 3/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 |
| Right lower limb | 24h | 3/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 | 0/3 |
Embodiment 7 accelerated test results
Get 3 batch samples, press commercially available back,, placed 6 months under relative humidity 75% ± 5% condition, carry out accelerated test, the results are shown in Table 10 40 ℃ ± 2 ℃ of temperature.
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Constant temperature by six months quicken to observe, and the 3 batches of injection andrographolide pH value and content are all qualified, and other every inspections are all up to specification.Sample is the censorship once more in 8th month after surpassing acceleration 6 months time limits of observation, and pH value and content are still more stable as a result, shows that the andrographolide injectable powder in the shady and cool dry preservation of locating, can keep steady quality 2 years effects in the phase.
Claims (10)
1, 'Yanhuning ' frozen-dried powder injection, it prepares by following primary raw material: andrographolide, ion buffering is to, antioxidant.
2, injectable powder as claimed in claim 1 is characterized in that, described ion buffering to be phosphate-buffered to, carbonate buffering to or amino acid salts cushion right.
3, injectable powder as claimed in claim 1 is characterized in that, described antioxidant is L-cysteine hydrochloride, L-cysteine or sodium sulfite.
4, injectable powder as claimed in claim 1 is characterized in that, described ion buffering is right to being phosphate-buffered, and described antioxidant is the L-cysteine hydrochloride.
5, injectable powder as claimed in claim 4, it is characterized in that this injectable powder is made by the primary raw material of following weight portion: andrographolide 720～880, sodium hydrogen phosphate 80.64～98.56, sodium dihydrogen phosphate 58.05～70.95, L-cysteine hydrochloride 4.41～8.36.
6, injectable powder as claimed in claim 5 is characterized in that, this injectable powder is made by the primary raw material of following weight portion: andrographolide 800, sodium hydrogen phosphate 89.6, sodium dihydrogen phosphate 64.5, L-cysteine hydrochloride 4.9～7.6.
7, a kind of method for preparing each described injection of claim 1～6, it comprises step: get andrographolide and dissolve with water for injection, regulate pH to 6.0～7.0, add the ion buffering to aqueous solution and antioxidant aqueous solution, handle with activated carbon adsorption, regulate pH to 6.3～7.1, benefit adds to the full amount of water for injection, and stirs the back lyophilizing promptly.
8, preparation method as claimed in claim 7, it is characterized in that, the method comprising the steps of: 45 ℃～60 ℃ the water for injection of measuring amount of preparation 70%, the andrographolide that adds recipe quantity while stirring, keep 45 ℃～60 ℃ of temperature, after treating all dissolvings, be cooled to room temperature immediately,, add the ion buffering aqueous solution with 10% sodium bicarbonate solution adjust pH to 6.0～7.0, stir evenly the active carbon that the back adds percentage by weight 0.2～1.0%, stirring and adsorbing 20 minutes, carbon removal is with 10% sodium bicarbonate solution adjust pH to 6.3～7.1, benefit adds to the full amount of water for injection, and stirs the back lyophilizing promptly.
9, preparation method as claimed in claim 8, it is characterized in that, the method comprising the steps of: measure 50 ℃～55 ℃ water for injection of amount of preparation 70%, add the andrographolide of recipe quantity while stirring, keep 50 ℃～55 ℃ of temperature, after treating all dissolvings, be cooled to room temperature immediately,, add the ion buffering aqueous solution and antioxidant aqueous solution with 10% sodium bicarbonate solution adjust pH to 6.6～6.8, stir evenly the active carbon that the back adds percentage by weight 0.4～0.7%, stirring and adsorbing 20 minutes, carbon removal is with 10% sodium bicarbonate solution adjust pH to 6.7～6.9, benefit adds to the full amount of water for injection, stir, be cooled to fine straining below 30 ℃, fill, half tamponade, lyophilizing, lid is rolled in tamponade, visual inspection, packing.
10, as each described preparation method of claim 7～9, it is characterized in that the omnidistance nitrogen filled protection of process for preparation.
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| CN101249079B (en) * | 2008-03-14 | 2010-11-17 | 重庆药友制药有限责任公司 | Andrographolide succinic acid half-ester natrium potassium salt and preparations |
| CN102552183A (en) * | 2012-02-02 | 2012-07-11 | 武汉长联来福制药股份有限公司 | Preparation method of potassium sodium dehydroaadroandrographolide succinate freeze-dried powder injection |
| CN102603684A (en) * | 2012-01-19 | 2012-07-25 | 黑龙江珍宝岛药业股份有限公司 | Sterile andrographolide and preparation method thereof |
| CN102614136A (en) * | 2012-04-18 | 2012-08-01 | 宁辉 | Potassium sodium dehydroandrographolide succinate composition for injection, and freeze-dried powder injection and preparation method for freeze-dried powder injection |
| CN104606148A (en) * | 2014-12-29 | 2015-05-13 | 重庆药友制药有限责任公司 | Potassium sodium dehydroandroan drographolide succinate preparation for injection and preparation method of potassium sodium dehydroandroan drographolide succinate preparation |
| CN104744412A (en) * | 2015-04-07 | 2015-07-01 | 重庆药友制药有限责任公司 | Dehydroandrographolide succinate compound |
| CN106420711A (en) * | 2016-10-11 | 2017-02-22 | 哈尔滨珍宝制药有限公司 | Andrographolide composition, injection preparation of andrographolide composition and preparation method |
| CN107184556A (en) * | 2017-06-13 | 2017-09-22 | 成都万维优方科技有限公司 | A kind of andrographolide lyophilized formulations and preparation method thereof |
| CN109674738A (en) * | 2019-01-21 | 2019-04-26 | 武汉长联来福制药股份有限公司 | Andrographolide preparation, patch and preparation method thereof |
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| CN101249079B (en) * | 2008-03-14 | 2010-11-17 | 重庆药友制药有限责任公司 | Andrographolide succinic acid half-ester natrium potassium salt and preparations |
| CN102603684A (en) * | 2012-01-19 | 2012-07-25 | 黑龙江珍宝岛药业股份有限公司 | Sterile andrographolide and preparation method thereof |
| CN102552183A (en) * | 2012-02-02 | 2012-07-11 | 武汉长联来福制药股份有限公司 | Preparation method of potassium sodium dehydroaadroandrographolide succinate freeze-dried powder injection |
| CN102614136A (en) * | 2012-04-18 | 2012-08-01 | 宁辉 | Potassium sodium dehydroandrographolide succinate composition for injection, and freeze-dried powder injection and preparation method for freeze-dried powder injection |
| CN102614136B (en) * | 2012-04-18 | 2013-05-08 | 宁辉 | Potassium sodium dehydroandrographolide succinate composition for injection, and freeze-dried powder injection and preparation method for freeze-dried powder injection |
| CN104606148A (en) * | 2014-12-29 | 2015-05-13 | 重庆药友制药有限责任公司 | Potassium sodium dehydroandroan drographolide succinate preparation for injection and preparation method of potassium sodium dehydroandroan drographolide succinate preparation |
| CN104606148B (en) * | 2014-12-29 | 2017-10-27 | 重庆药友制药有限责任公司 | A kind of Andrographolide in Andrographolide for Injection preparation and preparation method thereof |
| CN104744412A (en) * | 2015-04-07 | 2015-07-01 | 重庆药友制药有限责任公司 | Dehydroandrographolide succinate compound |
| CN106420711A (en) * | 2016-10-11 | 2017-02-22 | 哈尔滨珍宝制药有限公司 | Andrographolide composition, injection preparation of andrographolide composition and preparation method |
| CN107184556A (en) * | 2017-06-13 | 2017-09-22 | 成都万维优方科技有限公司 | A kind of andrographolide lyophilized formulations and preparation method thereof |
| CN109674738A (en) * | 2019-01-21 | 2019-04-26 | 武汉长联来福制药股份有限公司 | Andrographolide preparation, patch and preparation method thereof |
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