CN101596182A - 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 - Google Patents
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 Download PDFInfo
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Abstract
The present invention relates to a kind of lyophilized injectable powder, aqueous injection that contains pharmaceutical composition, its purposes and the preparation method of salviol acid A and contain said composition.The preparation method of this Pharmaceutical composition is as follows: get salviol acid A and be dissolved in or be scattered in water or the ethanol, one or more that get alkaline sodium, potassium salt are soluble in water, two kinds of solution are mixed, fully stirring clarifies them fully, conventional lyophilizing or evaporated under reduced pressure, that is, or directly make lyophilized injectable powder or aqueous injection with adding pharmaceutic adjuvant in the above-mentioned aqueous solution.Salvianolic acid A compositions provided by the invention stability in aqueous solution is strong, dissolubility is high, it is oxidized to be difficult for; Preparation method good manufacturability, simple to operate, production cost is low, can be used for preparing the medicine of controlling the news ischemic heart, cerebrovascular disease.Contain the salvianolic acid A compositions freeze-dried powder, liquid drugs injection good stability, uniformity height, meet the medicine requirement.
Description
Technical field
The present invention relates to a kind of medical composition and its use, said composition contains a certain proportion of salviol acid A alkalescence sodium or potassium salt, also relates to the preparation method of said composition, and the freeze-dried powder, the aqueous injection that contain this pharmaceutical composition.
Background technology
The phenolic acid compound of salviol acid A (Salvianolic acid A) for existing among the traditional Chinese medical science drug for invigorating blood circulation and eliminating stasis Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bge commonly used, natural content is about between 0.01%～0.08%, be that professor Li Lianniang of Beijing medicine institute at first finds [Li LN et al.Salvianolic acid A the earliest in Radix Salviae Miltiorrhizae, a new depsidefrom roots of Salviamiltiorrhiga, Planta Medica, 1984; 50:227] subsequently, water-soluble phenolic acid compounds in the discovery Radix Salviae Miltiorrhizaes such as professor Li Lianniang has antithrombotic, improve blood circulation, anti-oxidative damage, improve important biomolecule activity such as learning and memory, even more important for the quinoid diterpene-kind compound (is representative with Tanshinone I I A) than early discovery in the Radix Salviae Miltiorrhizae, more can represent a class natural product of Radix Salviae Miltiorrhizae function of promoting blood circulation to disperse blood clots.[institute of Materia Medica,Chinese Academy of Medical Sciences, Chinese herbal medicine modern study, P498～522, Beijing Medical University, combined publication society of China Concord Medical Science University 1996].Medical courses in general institute medicine research work show: in the Radix Salviae Miltiorrhizae total phenolic acids content the highest for salvianolic acid B, what anticoagulant and antioxidant activity were the strongest is salviol acid A.Subsequently, medicine institute of medical courses in general institute successfully develops Chinese medicine one kind new medicine salvianolic acid B through research and development for many years, is used for cardiovascular and cerebrovascular disease and transfers the possession of the production of sky, Tianjin Shi Li group.In addition, professor Zhu Dayuan of Shanghai medicine institute of the Chinese Academy of Sciences finds: phenolic acid compound mainly exists with the magnesium salt form in the Radix Salviae Miltiorrhizae, and successfully develop two class Chinese medicine Radix Salviae Miltiorrhizae total phenolic acids B and freeze-dried powders thereof, transferring sea green paddy Pharmaceutical produces, the product of green paddy is mainly based on the salvianolic acid B magnesium salt, chromatograph normalization content surpasses 90%, and product listing in 1 year has surpassed 4,000 ten thousand sales volumes.
The salviol acid A activity is higher than salvianolic acid B, and molecular weight is little by about 224.16 than the salvianolic acid B molecular weight, so easier permeable membrane enters cell, should there be better oral administration biaavailability and blood brain barrier transmitance the phase of giving, is the chemical compound that the treatment potentiality are more arranged than salvianolic acid B.
The water solublity of highly purified Radix Salviae Miltiorrhizae acid A can not be directly used in drug administration by injection less than 5mg/ml, and salviol acid A be the strongest known antioxidant at present, and its preparation stability is very difficult problem, and the stability of its injection water injection more is difficult to solution.Therefore obtaining stable, water-soluble salviol acid A preparation is the key issue that solves the clinical use limitation of salviol acid A.
Summary of the invention
The object of the present invention is to provide that a kind of stability is strong in aqueous solution, dissolubility is high, it is oxidized to be difficult for, can tolerate low temperature, pyritous salviol acid A compositions.
Another object of the present invention is to provide above-mentioned salviol acid A preparation method of composition.
A further object of the present invention provides a kind of good stability, uniformity height, meets the freeze-dried composition of medicine rehydration requirement.
A further object of the present invention provide a kind of can tolerate high temperature sterilize, clarity good, can room temperature preserve more than 2 years, meet the salviol acid A injection of injection requirement.
A further object of the present invention provides the lyophilized injectable powder that contains the salviol acid A pharmaceutical composition and the preparation method of aqueous injection.
A further object of the present invention provides and contains the salviol acid A pharmaceutical composition and be used to prepare the purposes for the treatment of cardiovascular and cerebrovascular diseases medicament.
The technical scheme that realizes goal of the invention is to solve like this:
Soluble in water alkaline sodium, potassium salt, salviol acid A is dissolved in or is scattered in water or the ethanol, two kinds of solution are mixed, fully stir it is reacted completely, to the solution clarification, conventional lyophilizing or evaporated under reduced pressure, promptly.Or in settled solution, directly add in antioxidant, chelating agen and the excipient one or more, make lyophilized injectable powder or aqueous injection by general preparation technology then.
Alkaline sodium or potassium salt be meant sodium citrate (potassium), sodium hydrogen phosphate (potassium), sodium benzoate (potassium), sodium succinate (potassium), sodium aminosalicylate (potassium), P-hydroxybenzoic acid sodium (potassium), neighbour, to a, sodium benzoate (potassium), neighbour, to ,-in oxybenzene sodium formate alkaline sodiums such as (potassium) or the potassium salt one or more.
The mol ratio of salviol acid A and alkaline sodium or potassium salt is: 1: 0.3-10.0.
Antioxidant is one or more in sodium sulfite, sodium sulfite, thiosulfuric acid hydrogen sodium or the vitamin C, and its consumption is clinical acceptable conventional amount used, is the 0.05-0.2% (w/v) of injection.
Chelating agen is that one or more its consumptions in ethylenediaminetetraacetic acid, disodiumedetate or the calcium disodium chelate are clinical acceptable conventional amount used, is the 0.001-1.0% (w/v) of injection.
Excipient is mannitol, sorbitol, sodium chloride, glucose, fructose, one or more in sucrose, xylitol, the lactose.
Than prior art, salviol acid A compositions of the present invention is than the big improve of the water solublity of salviol acid A own, stabilized aqueous solution, and low temperature is not separated out, and can tolerate high temperature sterilize, fulfilling medicinal requirements.Prepared freeze-dried powder and aqueous injection are placed stable, can satisfy clinical user demand.During use, interior sodium chloride injection or the glucose injection rapidly dissolvable of adding of freeze-dried composition that the present invention is prepared, the liquid drugs injection composition stable is good, so can use together in conjunction with sodium chloride injection or glucose injection.
Said composition rat heart ischemia/reperfusion injury and cerebral ischemia all have the better protect effect, and prompting can be used for the treatment of ischemic cardio cerebrovascular diseases.
Salviol acid A among the embodiment is separated acquisition by Shandong Target Drug Research Co., Ltd. process-scale chromatography research department in salviamiltiorrhizabung, its content of high performance liquid chromatogram external standard method is 98.5%.
The specific embodiment
Embodiment one: get salviol acid A 5.0g (0.01mol) and be dissolved in the 250ml ethanol, get sodium citrate 0.9803g (0.0033mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Lyophilizing promptly.
Embodiment two: take by weighing the salviol acid A compositions 5.98g that makes according to embodiment one and be dissolved in the 300ml water for injection, continue to stir to make fully and dissolve.Add 4.0g mannitol, 0.6g sodium sulfite, 0.6g calcium disodium chelate again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, packing, loading amount are every bottle and contain the 25mg salviol acid A, in-50～30 ℃ of lyophilizations, add a cover, seal, packing promptly gets freeze-dried powder.Embodiment three, get salviol acid A 5.0g (0.01mol) and be scattered in the 250ml water for injection, get sodium hydrogen phosphate 0.7099g (0.005mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 4.0g lactose, 0.6g sodium sulfite again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, packing, loading amount is every bottle and contains the 25mg salviol acid A, in-50～30 ℃ of lyophilizations, add a cover, seal, packing, promptly.
Embodiment four: get salviol acid A 5.0g (0.01mol) and be scattered in the 250ml water for injection, get sodium benzoate 1.411g (0.01mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 4.0g lactose, 0.6g sodium sulfite, disodiumedetate 0.6g again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, packing, loading amount are every bottle and contain the 25mg salviol acid A, in-50～30 ℃ of lyophilizations, add a cover, seal, packing, promptly.
Embodiment five: get salviol acid A 5.0g (0.01mol) and be dissolved in the 30ml medicinal alcohol, add 220ml water for injection again, stir, get potassium citrate 1.071g (0.0033mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 4.0g mannitol again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, and is fixed molten to 400ml, packing, loading amount is every bottle and contains the 25mg salviol acid A, in-50～30 ℃ of lyophilizations, adds a cover, seal, packing, promptly.
Embodiment six: get salviol acid A 5.0g (0.01mol) and be dissolved in the 30ml medicinal alcohol, add 220ml water for injection again, stir, get sodium benzoate 1.411g (0.01mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add the 4.0g glucose again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, and is fixed molten to 400ml, packing, loading amount is every bottle and contains the 25mg salviol acid A, in-50～30 ℃ of lyophilizations, adds a cover, seal, packing, promptly.
Embodiment seven: get salviol acid A 5.0g (0.01mol) and be scattered in the 250ml water for injection, get sodium citrate 0.9803g (0.0033mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 0.6g sodium sulfite and 0.6g calcium disodium chelate again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, fill the nitrogen packing, loading amount is every and contains the 25mg salviol acid A, sterilization, add a cover, seal, packing, promptly.
Embodiment eight: get salviol acid A 5.0g (0.01mol) and be dissolved in the 100ml medicinal alcohol, add 150ml water for injection again, stir, get sodium hydrogen phosphate 0.7099g (0.005mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 0.6g sodium sulfite and 0.6g calcium disodium chelate again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, fill the nitrogen packing, loading amount is every and contains the 25mg salviol acid A, sterilization, add a cover, seal, packing, promptly.
Embodiment nine: get salviol acid A 5.0g (0.01mol) and be dissolved in the 100ml medicinal alcohol, add 150ml water for injection again, stir, get sodium benzoate 1.411g (0.01mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add 0.6g sodium sulfite and 0.6g calcium disodium chelate again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, fixed molten to 400ml, fill the nitrogen packing, loading amount is every and contains the 25mg salviol acid A, sterilization, add a cover, seal, packing, promptly.
Embodiment ten: get salviol acid A 5.0g (0.01mol) and be dissolved in the 100ml ethanol, add 150ml water for injection again, stir, get potassium citrate 1.071g (0.0033mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add the 0.6g sodium sulfite again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, and is fixed molten to 400ml, fills the nitrogen packing, and loading amount is every and contains the 25mg salviol acid A that sterilization is added a cover, and seals, and packs, promptly.
Embodiment 11: get salviol acid A 5.0g (0.01mol) and be dissolved in the 50ml ethanol, add 200ml water for injection again, stir, get sodium benzoate 1.411g (0.01mol) and be dissolved in the 100ml water for injection, two kinds of solution are mixed, continue to stir 30min until reacting completely.Add the 0.6g sodium sulfite again, stirring and dissolving, the needle-use activated carbon stirring at normal temperature 30min of adding 0.35g filters, and is fixed molten to 400ml, fills the nitrogen packing, and loading amount is every and contains the 25mg salviol acid A that sterilization is added a cover, and seals, and packs, promptly.
Test example 1
This test example has been investigated salviol acid A and salviol acid A compositions (pressing embodiment 1 preparation) dissolubility
Press in note on the use of Chinese Pharmacopoeia (2005 editions) test method(s) operation about dissolubility.
Take by weighing the salviol acid A and the salviol acid A compositions that are ground into fine powder respectively, place the aqueous solution of 25 ± 2 ℃ of 25ml, in 30 seconds of strong jolting every 5 minutes, observe the dissolving situation in 30 minutes, as when not having visual visible particles of solute, promptly be considered as dissolving fully.
Measurement result
| 5mg/ml | 50mg/ml | 100mg/ml | |
| Salviol acid A | Insoluble particles is arranged | Insoluble particles is arranged | Insoluble particles is arranged |
| The salviol acid A compositions | Clear | Clear | Clear |
Conclusion: the dissolubility of salviol acid A in aqueous solution is less than 5mg/ml, and the dissolubility of salviol acid A compositions in aqueous solution is greater than 100mg/ml.
Test example 2
This test example has been investigated the protective effect of salvianolic acid A compositions to heart ischemia/reperfusion injury.Press the isolated rat heart method.The earlier logical N of anoxia perfusion group again
2Anoxia 45 minutes, normal perfusion was recovered 30 minutes in the back, compared with normal group, and myocardium malonaldehyde (MDA) content increases, and superoxide dismutase (SOD) is active to descend.(contain salvianolic acid A 20umol/L, 40umol/L), carry out anoxia then and irritate again, then show as myocardium MDA content and pour into obvious minimizing again, the SOD activity is also made moderate progress respectively at adding the salvianolic acid A compositions in the perfusate than anoxia.Illustrate that reperfusion injury has protective effect to the salvianolic acid A compositions to the heart anoxia.
The influence of cardiac muscle mda content and superoxide dismutase activity when the salvianolic acid A compositions is poured into the isolated rat heart anoxia again
Annotate: compare with normal control:
*P＜0.05,
*P＜0.01; Irritate ratio again with anoxia:
#P＜0.05,
##P＜0.01;
Test example 3
The salvianolic acid A compositions is to the influence of rat local cerebral ischemia damage.
1. divide into groups and experimental technique
The Wistar rat is divided into (1) sham operated rats (waiting the capacity solvent) at random, (2) model control group (waiting the capacity solvent), (3) salvianolic acid A group (6mg/kg, iv), (4) salvianolic acid A compositions low dose group (in salvianolic acid A, 3mg/kg, iv); (5) dosage group in the salvianolic acid A compositions (in salvianolic acid A, 6mg/kg, iv); (6) salvianolic acid A compositions high dose group (in salvianolic acid A, 12mg/kg, iv).Every group 10.After the fasting 12 hours, and chloral hydrate (350mg/kg, i.p.) anesthesia separates right carotid, and folder closes in the neck, common carotid artery, external carotid artery proximal part and distal end ligation, cut off the centre.The external carotid artery free-end is pulled to internal carotid artery in alignment, bolt line (selecting diameter 0.24mm nylon wire for use, length 5.0cm) is inserted into intracranial by external carotid artery, stop when meeting slight resistance, insertion depth is about 2cm.Ligation external carotid artery opening, and open the common carotid artery bulldog clamp, the disinfection and stitching wound causes left side middle cerebral artery ischemia model; Sham operated rats is only carried out the separation (above experiment is all carried out at 23 ℃～25 ℃) of right carotid, internal carotid artery, external carotid artery.Each treated animal intravenous injection relative medicine of postoperative.Press document [Liu Xiaoguang, Xu Lina, a kind of rat brain medium-sized artery model that can estimate thrombolytic and anti-thrombolytic after 24 hours, Acta Pharmaceutica Sinica, 1995,30:662] described method and standard is observed and the behavior disorder of record rat: (A) carry the Mus tail and observe forelimb flexing situation, stretch to ground as two forelimb symmetries, count 0 fen, the wrist flexing occurs as operation offside forelimb and count 1 fen, the elbow flexing is counted 2 fens, the shoulder inward turning is counted 3 fens, existing wrist flexing and/or elbow flexing have shoulder inward turning person again, count 4 fens.(B) animal is placed on the plane earth, push away both shoulders respectively, check resistance to side shifting.As bilateral resistance equity and strong, count 0 fen, as resistance descender when the operation offside promotes, according to decline degree difference be divided into gently, in, weigh three degree, count 1,2 and 3 fen respectively.(C) the two forelimbs of animal are put on the wire netting, observed the muscular tension of two forelimbs.Two muscle of anterior limb tension force equities and strong person count 0 fen.Count 1,2 and 3 fen according to operation offside muscular tension decline degree difference equally.(D) animal has ceaselessly to a side person of turn-taking, and counts 1 fen.According to the standard scoring, full marks are 11 minutes, and mark is high more, and expression animal behavior obstacle is serious more.
Put to death rat behind the behavior scoring, get brain, remove olfactory bulb, cerebellum and low brain stem, crownly be cut into 5, the brain sheet takes on a red color after normal structure is dyed with red tetrazolium (TTC) dyeing, and blocking tissue is white in color, taking a picture in dyeing back, asks the infarct size ratio with Chinese Aero-Space university pathological image analysis software.And survey cortex MDA content.
Data are represented with X ± s, carry out statistical procedures with t check between group.
2. result
It is as shown in the table, and ischemia is after 24 hours, and rat shows tangible behavior disorder, and tangible kitchen range shape ischemic region also appears in rat cerebral tissue, reaches about 25% of full brain; Give the salvianolic acid A combination of various dose, the animal behavior obstacle has alleviating in various degree, and the rat cerebral ischemia district also takes an evident turn for the better, and is dose dependent.Compared significant difference with the salvianolic acid A group.See following table for details.
The influence that the salvianolic acid A compositions is damaged the rat local cerebral ischemia (n=10, X ± s)
Annotate: compare with model control group
*P＜0.05,
*Compare with the salvianolic acid A group P＜0.01
#P＜0.05,
##P＜0.01.
Claims (9)
1, a kind of compositions that contains salviol acid A and alkaline sodium or potassium salt, it is characterized in that: the mol ratio of salviol acid A and alkaline sodium or potassium salt is: 1: 0.3-10.0.
2, according to the compositions described in the claim 1, it is characterized in that: alkaline sodium or potassium salt are selected from following one or more, sodium citrate (potassium), sodium hydrogen phosphate (potassium), sodium benzoate (potassium), sodium succinate (potassium), sodium aminosalicylate (potassium), P-hydroxybenzoic acid sodium (potassium), neighbour, to a, sodium benzoate (potassium), neighbour, to ,-oxybenzene sodium formate (potassium).
3, the preparation of compositions technology described in claim 1, it is characterized in that: get salviol acid A and be dissolved in or be scattered in water or the ethanol, one or more that get alkaline sodium or potassium salt are soluble in water, two kinds of solution are mixed, fully stirring clarifies them fully, conventional lyophilizing or evaporated under reduced pressure, promptly.
4, a kind of lyophilized injectable powder, aqueous injection is characterized in that: contain the compositions as claimed in claim 1 of therapeutic dose and proper quantity of antioxidant, chelating agen, excipient.
5, antioxidant as claimed in claim 4 is in sodium sulfite, sodium sulfite, thiosulfuric acid hydrogen sodium or the vitamin C one or more.
6, chelating agen as claimed in claim 4 is in ethylenediaminetetraacetic acid, disodiumedetate or the calcium disodium chelate one or more.
7, excipient as claimed in claim 4 is mannitol, sorbitol, sodium chloride, glucose, fructose, one or more in sucrose, xylitol, the lactose.
8, the preparation method of freeze-dried powder as claimed in claim 4, aqueous injection is characterized in that comprising the following steps:
The compositions of 1) weighing salviol acid A and alkaline sodium, potassium salt is dissolved in the suitable quantity of water; Or directly get salviol acid A and be scattered in the water, get alkaline sodium, potassium salt is soluble in water, with the two mixing, fully stir and make clarification;
2) one or more in adding proper quantity of antioxidant, chelating agen, the excipient;
3) filtration, packing;
4) get aqueous injection after the sterilization, or get freeze-dried powder after the lyophilizing.
9, the purposes of compositions as claimed in claim 1 in the preparation treatment ischemic heart, cerebrovascular disease medicament.
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100166800A CN101596182A (en) | 2008-06-05 | 2008-06-05 | 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 |
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| Application Number | Priority Date | Filing Date | Title |
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| CNA2008100166800A CN101596182A (en) | 2008-06-05 | 2008-06-05 | 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 |
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| CN102432467A (en) * | 2011-09-30 | 2012-05-02 | 吴谢军 | Salvianolic acid A magnesium salt, preparation method and use of the salvianolic acid A magnesium salt, and salvianolic acid A magnesium salt-containing freeze-dried powder injection composition |
| CN103006582A (en) * | 2012-11-20 | 2013-04-03 | 陆文萍 | Salvianolic acid A lyophilized powder injection and application thereof in preparation of drugs |
| CN103083257A (en) * | 2012-11-20 | 2013-05-08 | 陆文萍 | Salvianolic acid A freeze-dried powder injection and application thereof for preparing medicines |
| CN103142517A (en) * | 2012-11-20 | 2013-06-12 | 楚健 | Salvianolic acid A dropping pill and application thereof to medicine preparation |
| CN103816113A (en) * | 2012-11-19 | 2014-05-28 | 上海中西制药有限公司 | Salviae miltiorrhizae injection and preparation method thereof |
| CN104473883A (en) * | 2014-11-26 | 2015-04-01 | 中国人民解放军第四军医大学 | Acetyl tanshinol freeze-dried powder injection and preparation method thereof |
| CN105510495A (en) * | 2015-10-22 | 2016-04-20 | 中国药科大学 | Method for revealing pharmaceutically active ingredients and combinations of pharmaceutically active ingredients |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102432467A (en) * | 2011-09-30 | 2012-05-02 | 吴谢军 | Salvianolic acid A magnesium salt, preparation method and use of the salvianolic acid A magnesium salt, and salvianolic acid A magnesium salt-containing freeze-dried powder injection composition |
| CN103816113A (en) * | 2012-11-19 | 2014-05-28 | 上海中西制药有限公司 | Salviae miltiorrhizae injection and preparation method thereof |
| CN103816113B (en) * | 2012-11-19 | 2016-04-27 | 上海中西制药有限公司 | A kind of danshen-containing injections and preparation method thereof |
| CN103006582A (en) * | 2012-11-20 | 2013-04-03 | 陆文萍 | Salvianolic acid A lyophilized powder injection and application thereof in preparation of drugs |
| CN103083257A (en) * | 2012-11-20 | 2013-05-08 | 陆文萍 | Salvianolic acid A freeze-dried powder injection and application thereof for preparing medicines |
| CN103142517A (en) * | 2012-11-20 | 2013-06-12 | 楚健 | Salvianolic acid A dropping pill and application thereof to medicine preparation |
| CN103006582B (en) * | 2012-11-20 | 2015-02-18 | 江西青峰药业有限公司 | Salvianolic acid A lyophilized powder injection and application thereof in preparation of drugs |
| CN103142517B (en) * | 2012-11-20 | 2016-01-06 | 江西青峰药业有限公司 | A kind of salvianolic acid A drop pill and prepare medicinal usage |
| CN104473883A (en) * | 2014-11-26 | 2015-04-01 | 中国人民解放军第四军医大学 | Acetyl tanshinol freeze-dried powder injection and preparation method thereof |
| CN104473883B (en) * | 2014-11-26 | 2017-06-13 | 中国人民解放军第四军医大学 | A kind of acetyl danshensu freeze drying powder injection and preparation method thereof |
| CN105510495A (en) * | 2015-10-22 | 2016-04-20 | 中国药科大学 | Method for revealing pharmaceutically active ingredients and combinations of pharmaceutically active ingredients |
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