CN1762342A - Safflor yellow A-containing pharmaceutical composition, its preparation method and usage - Google Patents
Safflor yellow A-containing pharmaceutical composition, its preparation method and usage Download PDFInfo
- Publication number
- CN1762342A CN1762342A CN 200510109599 CN200510109599A CN1762342A CN 1762342 A CN1762342 A CN 1762342A CN 200510109599 CN200510109599 CN 200510109599 CN 200510109599 A CN200510109599 A CN 200510109599A CN 1762342 A CN1762342 A CN 1762342A
- Authority
- CN
- China
- Prior art keywords
- yellow
- pharmaceutical composition
- safflower yellow
- preparation
- safflower
- 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.)
- Pending
Links
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses a pharmaceutical composition which is a compound preparation prepared from aceglutamide and Safflomin A. The pharmaceutical composition can be used for treating cerebrovascular diseases, liver stupor, memory obstacle, coronary disease and vascular diseases.
Description
Technical field
The invention belongs to medical technical field, be specifically related to a kind of safflower yellow A pharmaceutical composition that contains, relate in particular to a kind of by aceglutamide and Flos Carthami flavochrome A, Flos Carthami makes the novel pharmaceutical combination thing of available dosage form with aceglutamide behind effective component extracting, its preparation method and the treatment obliterated cerebral vascular disease, the purposes of disease aspects such as the stupor that hepatic coma, hemiplegia, neurosurgery etc. cause, paralysis and the hypophrenia, memory disorder.
Background technology
Aceglutamide is N
2-acetyl-L-glutamine (C
7H
12N
2O
4), be white crystalline powder, the clinical cerebral function improving medicine that is commonly used for.This medicine can pass through blood-cerebrospinal fluid barrier, by be decomposed into glutamic acid after the blood-cerebrospinal fluid barrier, γ-An Jidingsuan (GABA) plays a role.Glutamic acid participates in central nervous system's information transmission, and Gabanergic antagonism glutamic acid irritability toxicological effect can improve the neurocyte metabolism, keeps the effect of neural stress ability and reduction blood ammonia, improves brain function.This clinical drug is usually used in stupor, paralysis and the hypophrenia that hepatic coma, hemiplegia, neurosurgery etc. cause, memory disorder etc.
Flos Carthami is the dried floral of feverfew Flos Carthami (Carthamus tinctorins L), and it is warm in nature, acrid in the mouth.The energy promoting blood circulation to restore menstrual flow, eliminating stasis to stop pain.Be used for menoxenia, dysmenorrhea and amenorrhea traumatic injury.Safflower yellow A (SY-A) is the effective ingredient that extracts from Flos Carthami, and it is one of important effective ingredient of Flos Carthami function of promoting blood circulation to disperse blood clots.In the treatment of diseases of cardiovascular and cerebrovascular systems, there had Flos Carthami injection to be used for to be clinical.Its technological standards is mainly with reference to 20 in ministry standard Chinese traditional patent formulation preparation: 108 pages of (WS
3-B-3825-98) produce.But the stability of Flos Carthami injection is defectiveness still, and the untoward reaction report is arranged.
Summary of the invention
An object of the present invention is to disclose a kind of safflower yellow A pharmaceutical composition that contains.
Another purpose of the present invention is to disclose the above-mentioned safflower yellow A preparation of drug combination method that contains.
Another object of the present invention is to disclose the above-mentioned purposes that contains the safflower yellow A pharmaceutical composition.
The object of the present invention is to provide a kind of pharmaceutical composition, the compound preparation that this pharmaceutical composition is formed by aceglutamide and Flos Carthami flavochrome A assembly.The general proportioning of this compound recipe is: aceglutamide weight is 10～500 times of safflower yellow A weight; Aceglutamide weight is that 50～200 times of safflower yellow A weight are better, research worker of the present invention is tested discovery in a large number, when aceglutamide weight in the pharmaceutical composition was 90～110 times of proportionings of safflower yellow A, synergism was best, curative effect is best, and experimental result sees Table 1.
The experiment of table 1 active component proportion optimization
| Aceglutamide: safflower yellow A (g/g) | Pharmacological action |
| 600∶1 500∶1 250∶1 200∶1 150∶1 110∶1 90∶1 50∶1 10∶1 5∶1 | ± + + ++ ++ +++ +++ ++ + ± |
Annotate: ± expression pharmacological action is poor; + expression pharmacological action is general; ++ the expression pharmacological action is better; +++expression pharmacological action is best.
Safflower yellow A of the present invention can prepare according to technique known, also can prepare with reference to following method:
(1) preparation of Carthamus yellow: the Flos Carthami crude drug adds the ethanol of water or 5%～95% or 10～200 times of volumes of mixed solvent of 5%～95% acetone solvent or three kinds of any ratios of solvent, 45～100 ℃, adopting frequency is that 900～2500 megahertzes, power are under 500～15000 watts the microwave action, extract 2～7 times, each 15～90 minutes, merge extractive liquid,, add the doubly acetone of amount of 10～70% (V/V) in the extracting solution, 0.05～5% crystallization auxiliary, left standstill 12～70 hours, separate out the mixed crystal of Carthamus yellow, promptly get Carthamus yellow.Crystallization auxiliary is selected from organic base or alkaloids, as triethanolamine, aconitine, Ramulus Uncariae cum Uncis alkali, ligustrazine, caffeine, matrine, kopsine, ergotin and salt, and as sodium citrate, sodium acetate, sodium bicarbonate, Disodium oxalate. etc.,
(2) preparation of safflower yellow A: following 4 kinds of any means all can obtain safflower yellow A, one, the macroporous resin of handling well on water-soluble or 0.1～15% ethanol of Carthamus yellow, with 5%, 15%, 30%, each 1～5 volume eluting of 45%, 60%, 75% and 90% ethanol, collect, merge 30% and 45% ethanol elution part, drying under reduced pressure promptly gets safflower yellow A; Its two, the sephadex lh-20 that balance is good on the water-soluble or methanol of Carthamus yellow, adopt water or methanol-water system (0: 100～100: 0) eluting, the component of collecting 1～5 column volume merges, drying under reduced pressure promptly gets safflower yellow A; Its three, good sephadex G-20, the water eluting of balance on the water-soluble or methanol of Carthamus yellow, the component of collecting 1～5 column volume merges, drying under reduced pressure promptly gets safflower yellow A; Its four, add 10%～30% ethyl acetate (V/V) in the Carthamus yellow, 10%～30% acetone (V/V), 0.05～5% crystallization auxiliary (reagent that W/V, assisting crystallisation separate out) left standstill 12～36 hours, separated out crystal, promptly got safflower yellow A.
Get gained safflower yellow A 10mg, be dissolved in 1ml ethanol, add a little magnesium powder jolting, drip several concentrated hydrochloric acid, it is not obvious to develop the color.Get gained safflower yellow A 1mg, be dissolved in 10ml methanol, 200～500nm carries out UV scanning, between 340～420nm (peak band I) and 220～270nm (peak band II) a strong absworption peak is arranged respectively, illustrates that this compounds belongs to chalcone compounds.Get gained safflower yellow A 1mg, be dissolved in 10ml methanol, drip on silica gel thin-layer plate, spray a small amount of bismuth potassium iodide, do not have yellow the appearance, the alkaloid feminine gender is described with capillary tube.Inanimate object alkali is residual in the crystallization.
The gained safflower yellow A adopts the HPLC method to detect, and (5 μ m, 4.6mm*250mm), mobile phase is water: acetonitrile: phosphoric acid (70: 30: 0.5), absorbing wavelength are λ=390nm to the ODS post, flow velocity 1ml/min.30 ℃ of column temperatures, its purity is more than or equal to 90%.
The safflower yellow A of this law gained promptly gets pharmaceutical composition of the present invention according to ratio mentioned above and acetyl paddy acyl ammonia proportioning.
Aceglutamide is the clinical cerebral function improving medicine that is commonly used in the pharmaceutical composition of the present invention, this medicine can pass through blood-cerebrospinal fluid barrier, by be decomposed into glutamic acid after the blood-cerebrospinal fluid barrier, γ-An Jidingsuan (GABA) plays a role, participate in central nervous system's information transmission, can improve the neurocyte metabolism, keep the effect of neural stress ability and reduction blood ammonia, improve brain function.Pharmaceutical composition of the present invention replenishes synergism heart and brain portion tissue mutually by the two, give full play to blood circulation promoting and blood stasis dispelling, improve brain function, improve the neurocyte metabolism, effect such as antithrombotic formation, microcirculation improvement, can be used as preparation treatment obliterated cerebral vascular disease, the application of disease medicament aspects such as the stupor that hepatic coma, hemiplegia, neurosurgery etc. cause, paralysis and the hypophrenia, memory disorder.Also can be used for preparing the application of disease medicament aspects such as treatment coronary heart disease, vasculitis.Through clinical experiment, the inventor finds, pharmaceutical composition provided by the invention has beyond thought breakthrough at clinical efficacy, simultaneously because safflower yellow A belongs to the chalcones material, its chemical stability is relatively poor, and the combination of this medicine is following to be found, the stability of Carthamus yellow all increases in following all preparations of this combination, and for the apoplexy depression good curative effect is arranged, this all is that the inventor is unexpected at first.
Pharmaceutical composition of the present invention can be prepared into the available dosage form on the various pharmaceuticss, as lyophilized injectable powder, tablet, drop pill, Sublingual tablet, dispersible tablet, capsule, granule, small-volume injection, bulk capacity injection, most preferred dosage form is a small-volume injection.The various dosage forms of pharmaceutical composition of the present invention can be according to the conventional production method preparation of pharmaceutical field.Such as using said composition to mix, be made into required dosage form then with one or more carriers.The selection of multiple dosage form helps the compliance of patient treatment, and the quality of life of improving patient has positive effect.
The present invention also provides this preparation of drug combination method.Weight portion of the present invention can be the known content units of field of medicaments such as μ g, mg, g, kg, and aceglutamide can adopt the raw material that meets medicinal standard.
Preferred pharmaceutical compositions small-volume injection specification of the present invention is 5ml, 10ml, 20ml, and every ml contains aceglutamide (C
7H
12N
2O
4) 30mg, after in addition every ml dilutes 500 times, be blank again with the distilled water, measure trap at 267 ± 1nm wavelength place, must not be lower than 0.3.Usage is as follows: intravenous drip, and a 5ml～20ml slowly instils with 5% or 10% glucose injection or 0.9% sodium chloride injection 250ml～500ml dilution back, and once-a-day, 10～15 days is a course of treatment.Pharmaceutical composition of the present invention is the compound preparation that safflower yellow A and aceglutamide form by the special ratios assembly, as preparation treatment obliterated cerebral vascular disease, the application of disease medicament aspects such as the stupor that hepatic coma, hemiplegia, neurosurgery etc. cause, paralysis and the hypophrenia, memory disorder.Also can be used for preparing the application of disease medicament aspects such as treatment coronary heart disease, vasculitis.
The specific embodiment
Further describe the present invention with embodiment below, help understanding, but described embodiment only is used to illustrate the present invention rather than restriction the present invention the present invention and advantage thereof, better effects if." contain the safflower yellow A pharmaceutical composition " hereinafter to be referred as " pharmaceutical composition " among the present invention.
Embodiment 1-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 30 times of volumes (W/V) 15%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary caffeine (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.The macroporous resin of handling well on water-soluble or 0.1～15% ethanol of Carthamus yellow, with each 3 volume eluting of 5%, 15%, 30%, 45%, 60%, 75% and 90% ethanol, collect, merge 30% and 45% ethanol elution part, drying under reduced pressure promptly gets safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
Embodiment 2-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 50 times of volumes 30%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary triethanolamine (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.The sephadex lh-20 that balance is good on the water-soluble or methanol of Carthamus yellow, adopt water or methanol-water system (50: 50) eluting, the component of collecting 1～2 column volume merges, and drying under reduced pressure promptly gets safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
Embodiment 3-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 100 times of volumes (W/V) 45%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary kopsine (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.Good sephadex G-20, the water eluting of balance on the water-soluble or methanol of Carthamus yellow, the component of collecting 1～1.5 column volume merges, and drying under reduced pressure promptly gets safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
Embodiment 4-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 200 times of volumes (W/V) 60%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary Ramulus Uncariae cum Uncis alkali (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.Add 10%～30% ethyl acetate (V/V) in the Carthamus yellow, 10%～30% acetone (V/V), 0.05～5% crystallization auxiliary calcium sulfate (reagent that W/V, assisting crystallisation separate out) left standstill 12～36 hours, separated out crystal, promptly got safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
Embodiment 5-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 60 times of volumes (W/V) 75%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary ligustrazine (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.The macroporous resin of handling well on water-soluble or 0.1～15% ethanol of Carthamus yellow, with each 3 volume eluting of 5%, 15%, 30%, 45%, 60%, 75% and 90% ethanol, collect, merge 30% and 45% ethanol elution part, drying under reduced pressure promptly gets safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
Embodiment 6-preparation of drug combination
The Flos Carthami crude drug adds the ethanol solvent of 50 times of volumes (W/V) 90%, adopting frequency is that 1100 megahertzes, power are 12000 watts microwave action, extract 5 times under 70 ℃ of conditions, each 50 minutes, merge extractive liquid, added 30% acetone (V/V) in the extracting solution, 0.3% crystallization auxiliary Disodium oxalate. (W/V, the reagent that assisting crystallisation is separated out), left standstill 36 hours, separate out crystal and be Carthamus yellow.The macroporous resin of handling well on water-soluble or 0.1～15% ethanol of Carthamus yellow, with each 3 volume eluting of 5%, 15%, 30%, 45%, 60%, 75% and 90% ethanol, collect, merge 30% and 45% ethanol elution part, drying under reduced pressure promptly gets safflower yellow A.
According to aceglutamide weight is that 100 times of safflower yellow A carry out proportioning, promptly.
The preparation of the bulk capacity injection of embodiment 7-pharmaceutical composition
Take by weighing aceglutamide (C
7H
12N
2O
4) 1500g, and be made into the 50000ml medicinal liquid by 15g safflower yellow A (according to embodiment 1 preparation), finally make 500 bottles of bulk capacity injections (specification is the 100ml/ bottle).
In dense preparing tank, add an amount of 80 ℃ of waters for injection, in dense preparing tank, drop into 360g sodium chloride, add safflower yellow A again, fully stir and make, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added in dilute preparing tank and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 5.6 ± 0.2, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is filled nitrogen by bottle during embedding in the 100ml infusion bottle, sterilization, promptly.
The preparation of the small-volume injection of embodiment 8-pharmaceutical composition
Take by weighing aceglutamide (C
7H
12N
2O
4) 150g, can be made into the 5000ml medicinal liquid with 1.5g safflower yellow A (according to embodiment 2 preparations), finally make 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, in dilute preparing tank, add and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add active carbon, left standstill 20 minutes by 0.02% of preparation cumulative volume, add water for injection to the dosing amount, transferring PH is 5.5 ± 0.1, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in the 5ml ampoule, ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the small-volume injection of embodiment 9-pharmaceutical composition
Take by weighing aceglutamide (C
7H
12N
2O
4) 150g, can be made into the 5000ml medicinal liquid with 1.5g safflower yellow A (according to embodiment 3 preparations), finally make 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 88 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, in dilute preparing tank, add and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add active carbon, left standstill 20 minutes by 0.02% of preparation cumulative volume, add water for injection to the dosing amount, transferring PH is 5.7 ± 0.1, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in the 5ml ampoule, ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the small-volume injection of embodiment 10-pharmaceutical composition
Take by weighing aceglutamide (C
7H
12N
2O
4) 150g, can be made into the 5000ml medicinal liquid with 1.5g safflower yellow A (according to embodiment 4 preparations), finally make 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 88 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, in dilute preparing tank, add and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add active carbon, left standstill 20 minutes by 0.02% of preparation cumulative volume, add water for injection to the dosing amount, transferring PH is 5.7 ± 0.1, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in the 5ml ampoule, ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the lyophilized injectable powder of embodiment 11-pharmaceutical composition
Take by weighing aceglutamide (C
7H
12N
2O
4) 75g, can be made into the 2500ml medicinal liquid with 0.75g safflower yellow A (according to embodiment 4 preparations), finally make 1000 of lyophilized injectable powders.
In dense preparing tank, add an amount of 80 ℃～90 ℃ waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, in dilute preparing tank, add and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add the Dextran 40 excipient, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, add water for injection to the dosing amount, transferring PH is 5.5～5.8, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, medicinal liquid fill behind end-filtration (loading amount 2.5ml/ props up), lyophilizing behind the false add plug, promptly.
The preparation of the tablet of embodiment 12-pharmaceutical composition
Aceglutamide (C
7H
12N
2O
4) 150g and Flos Carthami flavochrome A (according to embodiment 5 preparations) the abundant mixing of 1.5g, make and finally make 1000 in tablet.
Safflower yellow A, aceglutamide and 80 gram starch mixings with recipe quantity add the 20g10% starch slurry, cross 20 mesh sieves and granulate, and drying is crossed 20 mesh sieve granulate, adds 0.5 gram magnesium stearate compacting in flakes, promptly gets tablet.
The capsular preparation of embodiment 13-pharmaceutical composition
With 2g safflower yellow A (according to embodiment 6 preparations), pulverize back and aceglutamide (C
7H
12N
2O
4) 200g preparation finally makes 1000 of capsules.
Behind recipe quantity safflower yellow A and aceglutamide and 40g starch, 3g magnesium stearate mixing, cross 100 mesh sieves, encapsulated, promptly.
The preparation of the drop pill of embodiment 14-pharmaceutical composition
200g Polyethylene Glycol PEG600,100g Polyethylene Glycol PEG400,500g aceglutamide (C
7H
12N
20
4) 1 and 5g safflower yellow A (according to embodiment 1 preparation) make 10000 of drop pill.
Recipe quantity Polyethylene Glycol PEG600 and Polyethylene Glycol PEG400 under 70～80 ℃ of conditions in heating and melting, the aceglutamide and Flos Carthami flavochrome A that adds recipe quantity is abundant, stir, keep molten condition, by the dropper of internal diameter 9mm, external diameter 9.8mm, splash in the liquid Paraffin condensed fluid with the speed of 80 of per minutes, be condensed into ball, fling to surperficial liquid Paraffin, promptly.
The preparation of the Sublingual tablet of embodiment 15-pharmaceutical composition
Aceglutamide (C
7H
12N
2O
4) 1500g, safflower yellow A (according to embodiment 5 preparations) 15g, carboxymethyl starch sodium 100g, mannitol 500g and the abundant mixing of silicon dioxide 50g, add 5% polyvinylpyrrolidone rubber cement and granulate drying, granulate adds the 5g magnesium stearate, tabletting, make 1000 of Sublingual tablets, promptly.
The preparation of the bulk capacity injection of Comparative Examples 1 safflower yellow A
15g safflower yellow A (according to Comparative Examples 1 preparation) is made into the 50000ml medicinal liquid, finally makes 500 bottles of bulk capacity injections (specification is the 100ml/ bottle).
In dense preparing tank, add an amount of 80 ℃ of waters for injection, drop into 360g sodium chloride in dense preparing tank, add safflower yellow A again, fully stirring makes, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, fully stir and make dissolving fully, add active carbon, left standstill 20 minutes by 0.02% of preparation cumulative volume, add water for injection to the dosing amount, transferring PH is 5.6 ± 0.2, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in the 100ml infusion bottle, fill nitrogen by bottle during embedding, sterilization, promptly.
The preparation of the small-volume injection of Comparative Examples 2-safflower yellow A
1.5g safflower yellow A (according to Comparative Examples 2 preparations) can be made into the 5000ml medicinal liquid, finally makes 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 85 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon, heat 90 ℃ by 0.04% of preparation cumulative volume, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is fully stirred and makes dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 5.5 ± 0.1, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is in the 5ml ampoule, and ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the small-volume injection of Comparative Examples 3-safflower yellow A
1.5g safflower yellow A (according to embodiment 3 preparations) can be made into the 5000ml medicinal liquid, finally makes 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 88 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon, heat 90 ℃ by 0.04% of preparation cumulative volume, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is fully stirred and makes dissolving fully, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, and added water for injection to the dosing amount, transferring PH is 5.7 ± 0.1, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, and embedding is in the 5ml ampoule, and ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the small-volume injection of Comparative Examples 4-safflower yellow A
1.5g safflower yellow A (according to Comparative Examples 4 preparations) can be made into the 5000ml medicinal liquid, finally makes 1000 of small-volume injections (specification is that 5ml/ props up).
In dense preparing tank, add an amount of 88 ℃ of waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, with the medicinal liquid decarbonization filtering to dilute preparing tank, in dilute preparing tank, add and used the dissolved aceglutamide of an amount of NaOH, fully stir and make dissolving fully, add active carbon, left standstill 20 minutes by 0.02% of preparation cumulative volume, add water for injection to the dosing amount, transferring PH is 5.7 ± 0.1, and with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, embedding is in the 5ml ampoule, ampoule fills nitrogen by propping up during embedding, sterilization, promptly.
The preparation of the lyophilized injectable powder of Comparative Examples 5-safflower yellow A
0.75g safflower yellow A (according to embodiment 4 preparations) can be made into the 2500ml medicinal liquid, finally makes 1000 of lyophilized injectable powders.
In dense preparing tank, add an amount of 80 ℃～90 ℃ waters for injection, in dense preparing tank, add safflower yellow A, fully stir, add active carbon by 0.04% of preparation cumulative volume, heat 90 ℃, be incubated 20 minutes, be cooled to 50 ℃, the medicinal liquid decarbonization filtering to dilute preparing tank, is added the Dextran 40 excipient, add active carbon by 0.02% of preparation cumulative volume, left standstill 20 minutes, add water for injection to the dosing amount, transferring PH is 5.5～5.8, with the medicinal liquid decarbonization filtering, medicinal liquid is again through end-filtration, medicinal liquid fill behind end-filtration (loading amount 2.5ml/ props up), lyophilizing behind the false add plug, promptly.
The preparation of the tablet of Comparative Examples 6-safflower yellow A
1.5g safflower yellow A (according to embodiment 5 preparations) the abundant mixing of 10g is made and is finally made 1000 in tablet.
Safflower yellow A, aceglutamide and 80 gram starch mixings with recipe quantity add the 20g10% starch slurry, cross 20 mesh sieves and granulate, and drying is crossed 20 mesh sieve granulate, adds 0.5 gram magnesium stearate compacting in flakes, promptly.
The capsular preparation of Comparative Examples 7-safflower yellow A
With 2g safflower yellow A (according to embodiment 6 preparations), pulverize back and aceglutamide (C
7H
12N
2O
4) 200g preparation finally makes 1000 of capsules.
Behind recipe quantity safflower yellow A and aceglutamide and 40g starch, 3g magnesium stearate mixing, cross 100 mesh sieves, encapsulated, promptly.
The preparation of the drop pill of Comparative Examples 8-safflower yellow A
200g Polyethylene Glycol PEG600,100g Polyethylene Glycol PEG400 and 5g safflower yellow A (according to embodiment 1 preparation) are made 10000 of drop pill.
Recipe quantity Polyethylene Glycol PEG600 and Polyethylene Glycol PEG400 under 70～80 ℃ of conditions in heating and melting, the safflower yellow A that adds recipe quantity, stir, keep molten condition, by the dropper of internal diameter 9mm, external diameter 9.8mm, splash in the liquid Paraffin condensed fluid with the speed of 80 of per minutes, be condensed into ball, fling to surperficial liquid Paraffin, promptly.
The preparation of the Sublingual tablet of Comparative Examples 9-safflower yellow A
Safflower yellow A (according to embodiment 5 preparations) 1.5g, carboxymethyl starch sodium 100g, mannitol 500g and the abundant mixing of silicon dioxide 50g add 5% polyvinylpyrrolidone rubber cement and granulate drying, granulate adds the 5g magnesium stearate, tabletting, make 1000 of Sublingual tablets, promptly.
The investigation of experimental example 1-drug combination preparation stability
1. test method: the sample of getting each embodiment and reference examples places 40 ℃ calorstat to place 6 months, respectively at the content of safflower yellow A in 0 month, March, June sampling and measuring sample.
2. working sample is handled:
Every kind of sample got 10 packings separately, adds the suitable quantity of water dissolving respectively, and transfers to fully in the measuring bottle of suitable size, thin up is to scale, shake up, make the concentration that contains safflower yellow A and be about 0.5～5 μ g/ml, promptly can be used as the need testing solution of measuring safflower yellow A.Same method, water is prepared the reference substance solution that the concentration that contains safflower yellow A is about 0.5～5 μ g/ml.
3. assay method: each composition in the sample is measured according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2005).
4. result processing method: the amount of measuring safflower yellow A in the sample of each embodiment and reference examples in order to last method, with 0 month absolute content was the relative percentage composition of benchmark 100%, with the absolute content in March or June absolute content, be the relative percentage composition (%) in March or June divided by 0 month.
5. result of the test: the sample of each embodiment and reference examples places 40 ℃ calorstat to place 6 months, and the relative percentage composition of three kinds of vitamin B group when March, June the results are shown in Table 1.Embodiment 7 is identical in the technology of Comparative Examples 1, below analogizes.
The sample of table 1 embodiment and reference examples is at the relative percentage composition (%) in 40 ℃ of * March, 40 ℃ of * June
| Sample | Safflower yellow A | Sample | Safflower yellow A | ||
| 40 ℃ of * March (%) | 40 ℃ of * June (%) | 40 ℃ of * March (%) | 40 ℃ of * June (%) | ||
| Embodiment 7 | 96.6 | 94.7 | Comparative Examples 1 | 96.0 | 92.4 |
| Embodiment 8 | 97.5 | 95.6 | Comparative Examples 2 | 95.4 | 91.1 |
| Embodiment 9 | 98.8 | 96.7 | Comparative Examples 3 | 96.9 | 93.3 |
| Embodiment 10 | 98.2 | 96.0 | Comparative Examples 4 | 96.1 | 90.6 |
| Embodiment 11 | 96.4 | 94.6 | Comparative Examples 5 | 95.7 | 91.5 |
| Embodiment 12 | 95.9 | 93.8 | Comparative Examples 3 | 95.0 | 93.1 |
| Embodiment 13 | 97.6 | 95.4 | Comparative Examples 3 | 96.1 | 92.4 |
| Embodiment 14 | 97.1 | 94.2 | Comparative Examples 4 | 92.1 | 90.4 |
| Embodiment 15 | 96.6 | 94.7 | Comparative Examples 5 | 92.5 | 90.5 |
As seen the result compares with the sample of reference examples from table, and the stability of pharmaceutical composition safflower yellow A is significantly improved.
The detection of injection inspection items such as the appearance character of experimental example 2-pharmaceutical composition small-volume injection (according to embodiment 8-10 preparation), pH value, residue on ignition, heavy metal, protein, pyrogen.
Character this product is that yellowish red color is to henna clear liquid.
PH value 5.0～7.0 (two appendix VI of Chinese Pharmacopoeia version in 2000).
Residue on ignition is got this product 10ml, puts in the crucible of constant weight, measures (appendix IX J) in accordance with the law, leaves over residue and is no more than 2.0% (g/ml).
Heavy metal is got the residue of leaving under the residue on ignition item, adds nitric acid 2.5ml, and evaporate to dryness after eliminating to the nitrogen oxide steam, is put coldly, adds hydrochloric acid 2ml, puts in the water-bath behind the evaporate to dryness, and residue adds water to be made dissolving and move in the 10ml volumetric flask, adds water to scale, shakes up.Precision is measured 1ml and is added water 15ml, drips ammonia solution to instructions phenolphthalein solution is shown neutral, adds acetate buffer (pH3.5) 2ml again, after the slight fever dissolving, moves in the nessler colorimetric tube, and thin up becomes 25ml as sample cell.Other gets the reagent of preparation need testing solution, puts evaporate to dryness in the porcelain dish, and residue adds acetate buffer (pH3.5) 2ml and water 15ml, after the slight fever dissolving, move in the nessler colorimetric tube, add standard lead solution 1ml, thin up becomes 25ml again, adds thioacetamide test solution 2ml again in two pipes respectively, shakes up, placed 2 minutes, with putting on the blank sheet of paper, supreme downward perspective, color of showing in the sample cell and control tube are relatively, must not be darker, promptly contain heavy metal and do not cross 10/1000000ths.
Pyrogen is got this product, checks (two appendix XI of Chinese Pharmacopoeia version in 2000 D) in accordance with the law, and dosage is by the every 1kg injection of rabbit body weight 2ml, and is up to specification.
Protein is got this product 1ml, adds 30% sulfosalicylic acid test solution 1ml of new configuration, and mixing was placed 5 minutes, does not occur muddy.
Other meet relevant every regulation (2000 editions two appendix IB of Chinese Pharmacopoeia) under the injection item.
The aceglutamide content quantitative is measured in the experimental example 3-pharmaceutical composition small-volume injection (according to embodiment 8-10 preparation)
Aceglutamide assay: measure according to high performance liquid chromatography (two appendix VD of Chinese Pharmacopoeia version in 2000).
Chromatographic condition and system suitability test are filler with octadecylsilane chemically bonded silica; (regulating pH value 3.5 with triethylamine)-methanol (95: 5) is mobile phase with 0.2% phosphoric acid solution; The detection wavelength is 210nm.Number of theoretical plate calculates by the aceglutamide peak and is not less than 2500, and every ml contains aceglutamide (C
7H
12N
2O
4) should be 27mg～33mg.
Algoscopy: it is an amount of to get this product, accurately claims surely, with the mobile phase dissolving, and quantitatively is diluted to the solution that contains aceglutamide 0.1mg among every 1ml, as need testing solution, gets 20 μ l and injects chromatograph of liquid, the record chromatogram; It is an amount of that precision takes by weighing the aceglutamide reference substance in addition, makes the solution that contains 0.1mg among every 1ml approximately with mobile phase dissolving and dilution, and product solution is measured with method in contrast, presses external standard method with calculated by peak area.
The clinical verification of experimental example 4-pharmaceutical composition small-volume injection
The clinical verification of pharmaceutical composition small-volume injection treatment paralysis
1. clinical data
Totally 40 routine patients are my the department of cerebral surgery inpatient of institute, wherein male 24 examples, women 16 examples; Minimum 18 years old of age, maximum 78 years old, time 56.4 years old mean age all Drug therapy such as falls cranium pressure, hemostasis, antiinflammatory and improves that brain generation penetrates in conventional dehydration after the morbidity and begins after 2 weeks, the case of being admitted to hospital is divided into 2 groups at random, each 20 example, matched group and treatment group age, sex, the cause of disease, muscular strength are similar, and comparability is arranged.
2 Therapeutic Method
The treatment group: pharmaceutical composition small-volume injection (according to embodiment 9 preparation) intravenous drip, a 10～30ml slowly instils with 0.9% sodium chloride injection 500ml dilution back, once-a-day, person's routine anti symptom treatment that has the simultaneous phenomenon.
Matched group: the Flos Carthami injection intravenous drip, a 10～30ml slowly instils with 0.9% sodium chloride injection 500ml dilution back, once-a-day, the conventional anti symptom treatment of person that has the simultaneous phenomenon.
3 therapeutic outcomes
3.1 criterion of therapeutical effect
According to 0～5 grade of muscular strength staging, treatment back muscular strength rise 2 ranks or above be produce effects, 1 rank is effective, no changer is invalid.
3.2 statistical method: data result is checked with X, and P＜0.05 thinks that there were significant differences.
3.3 result
The contrast of table 1 pharmaceutical composition small-volume injection treatment hemiplegia
| Group | n | Produce effects | Effectively | Invalid | Total effective rate % |
| Treatment group matched group | 20 20 | 13 9 | 6 5 | 1 6 | 95.0％ 70.0％ |
Treatment group curative effect obviously is better than matched group, and difference has the significance meaning, P＜0.05.
4. conclusion
Hemiplegia is common in cerebral hemorrhage or serious cranium brain injury patient, especially after opening cranium volume temporo top clearance of intracerebral hematoma, cerebral edema disappears substantially, and muscular strength does not still have the general weak curative effect of obvious recuperator, and the time is longer, and especially muscular strength person's conventional therapy below 1 grade effect is all not obvious.This therapy pharmaceutical composition small-volume injection is as injectable drug, and is evident in efficacy, especially to can yet be regarded as a kind of method of uniqueness of serious hemiptegic.
The pharmaceutical composition small-volume injection illustrates the reasonability of its technology than the yield rate height of Flos Carthami injection, and also the stability of reactor product is better indirectly, and untoward reaction will be less.
The clinical verification of experimental example 5-pharmaceutical composition small-volume injection
The pharmaceutical composition small-volume injection is used for the treatment of coronary heart disease.
1. physical data:
Be total to diagnosis and treatment patients with coronary heart disease 80 examples, wherein male 48 examples, women 32 examples; Age 40-49 year 10 examples, 50-59 year 46 examples, 60-70 year 24 examples.Diagnostic criteria for coronary heart disease all meets WHO " about the name and the diagnostic criteria of ischemic heart desease " in 1979.Picked at random 80 routine patients are divided into treatment group 40 example and matched group 40 examples.
2. Therapeutic Method:
2.1 treatment group: pharmaceutical composition small-volume injection (according to embodiment 9 preparation) intravenous drip, a 10～30ml slowly instils with 0.9% sodium chloride injection 500ml dilution back, once-a-day, person's routine anti symptom treatment that has the simultaneous phenomenon.
2.2 matched group: oral sorbitrate 10mg time, 3 times on the 1st; Nifedipine 10mg time, 3 times on the 1st.7 days 1 courses of treatment, serve on 2 courses of treatment.
3. observe the symptoms before and after the medication as a result, sign and electrocardiogram situation of change, to judge curative effect.
3.1 curative effect determinate standard:
3.1.1 chest pain, cardio palmus shape disappear substantially, electrocardiogram shows that it normally is produce effects that ischemic state is recovered substantially;
3.1.2 chest pain, cardiopalmus sx or attack times reduce, electrocardiogram shows that myocardial ischemia is improved as effectively;
Symptom does not have obvious improvement after 2 weeks 3.1.3 take medicine, and electrocardiogram shows that ischemic state does not take a favorable turn to invalid.
3.2 therapeutic outcome
Treatment group produce effects 20 examples, effective 15 examples, invalid 4 examples, total effective rate is 90%.Matched group produce effects 22 examples, effective 8 examples, invalid 10 examples, total effective rate is 75%.
Clinical observation result shows that drop pill treatment coronary heart disease total effective rate of the present invention is 90%, and matched group is 75%, and aspect improving clinical symptoms and recovering the heart and gallbladder ischemic state, the treatment group is better than matched group, and does not see obvious toxic-side effects.
The clinical verification of experimental example 6-pharmaceutical composition Sublingual tablet
Experiment purpose: the pharmaceutical composition Sublingual tablet is used for anginal treatment.
Angina pectoris is the Vasculocardiology Deparment emergency case, and Yin Qiyi develops into sudden death, can reduce coronary heart disease accident incidence rate so effectively control angina pectoris.
1 data and method
1.1 case is collected patient with angina pectoris 56 examples of being in hospital, male 34 examples, women 22 examples, average year 54.9 ± 10.1 years old; Two groups of indifferences on sex, age and the course of disease, p＞0.05.28 examples are organized in treatment, matched group 28 examples.
1.2 anginal diagnostic criteria:
1. typical angina pectoris symptom appears during rest.
2. occurring angina pectoris companion reversibility ST section during light activity raises or reduces 〉=0.1mV.
3. single angina pectoris attacks time 〉=20 minute, 2 times of creatine phosphokinase-isozyme (CK-MB)＜upper limits of normal.
2. Therapeutic Method:
2.1 matched group: oral nitrate esters, calcium antagonist, beta-blocker and aspirin, be 15 days the course of treatment.The treatment group: take pharmaceutical composition Sublingual tablet (according to embodiment 15 preparations), 4 times on the one, each 1～2, sublingual administration, be 15 days the course of treatment.
2.2 observation index: observe treatment front and back angina pectoris attacks number of times, pain intensity and persistent period, blood pressure, heart rate, blood fat, ECG change, calculating systolic pressure and heart rate product.
2.3 curative effect judging standard:
2.3.1 the fatigue angina pectoris symptom improves 〉=2 grades, electrocardiogram recovers normal or ischemic ST descends, and recovery 〉=0.01mV is a produce effects.
Recover 0.05～0.10mV 2.3.2 1 grade of doing well,improving, ischemic ST descend, spontaneous angina pectoris angina pectoris under original living habit is controlled, and the angina pectoris number of times reduces, and electrocardiogram is improved as effectively.
2.3.3 do not reach above standard person for invalid.
3. result
2.1 two groups of efficacy analysis: treatment group total effective rate is 89.29%, matched group total effective rate 60.71%, and the two is p＜0.05 relatively, and significant difference is arranged, and sees Table 1
Table 1 liang group UA curative effect relatively
| Group | The example number | Produce effects | Effectively | Invalid | Total effective rate (%) |
| Treatment group matched group | 28 28 | 8 6 | 17 11 | 3 11 | 89.29 60.71 |
4. conclusion
The pharmaceutical composition Sublingual tablet is better than current conventional treatments to anginal therapeutic effect.
The clinical verification of experimental example 7-pharmaceutical composition small-volume injection
It is generally acknowledged the depressive anxiety of caused by cerebrovascular disease mental disorder based on affective disorder.It is 20%～60% that the depressed incidence rate of report post-stroke 1 year is arranged, so post-stroke depression (PSD) become important Mental health problems, and its prognosis directly has influence on patient's quality of life and functional rehabilitation.Adopt pharmaceutical composition small-volume injection treatment PSD, observe its curative effect and safety, now the result is reported as follows.
1 object and method
1.1 object of study: go into the group standard for to make a definite diagnosis through head CT or magnetic resonance examination, meet Chinese mental disorder classification and the diagnostic criteria of diagnostic criteria (CCMD-3) cerebral organic psychosis depressive state, 17 depressed rating scales of Han Midun (HAMD) scoring was greater than 18 minutes.Inpatient's 15 examples, male's 10 examples, women's 5 examples, age 50-75 year, average 63.2 years old.
1.2 Therapeutic Method:
Pharmaceutical composition small-volume injection (according to embodiment 9 preparation) intravenous drip, a 10～30ml slowly instils with 0.9% sodium chloride injection 500ml dilution back, once-a-day, person's routine anti symptom treatment that has the simultaneous phenomenon.
Adopt HAMD side reaction scale before treatment and treatment evaluate curative effect 1,2,4 weekends and subtract the branch evaluation by HAMD.
| Time | Before the treatment | Treated for 1 weekend | Treated for 2 weekends | Treated for 4 weekends |
| The HAMD scoring | 29.6±0.36 | 23.4±0.58 | 18.1±0.72 | 13.2±0.68 |
2 conclusions
The depressed rating scale of patient Han Midun (HAMD) scoring significantly descends after making the pharmaceutical composition small-volume injection, illustrates that this medicine post-stroke depression (PSD) also has better curative effect.
Claims (8)
1. one kind contains the safflower yellow A pharmaceutical composition, it is characterized in that, described pharmaceutical composition comprises aceglutamide and safflower yellow A, and its proportioning is: aceglutamide weight is 10～500 times of safflower yellow A weight.
2. pharmaceutical composition according to claim 1 is characterized in that, wherein said aceglutamide weight is 50～200 times of safflower yellow A weight, preferred 90～110 times.
3. pharmaceutical composition according to claim 1 and 2 is characterized in that, described safflower yellow A prepares in accordance with the following methods:
The Flos Carthami crude drug adds solvent and carries under microwave action, extracting solution, add acetone and crystallization auxiliary in the extracting solution, leave standstill, separate out the mixed crystal of Carthamus yellow, obtain Carthamus yellow, Carthamus yellow passes through macroporous resin column chromatography or sephadex lh-20 column chromatography or sephadex G-20 column chromatography or method for crystallising again and obtains safflower yellow A.
4. pharmaceutical composition according to claim 3 is characterized in that, described safflower yellow A prepares in accordance with the following methods:
(1) preparation of Carthamus yellow: the Flos Carthami crude drug adds the ethanol of water or 5%～95% or 10～200 times of volumes of mixed solvent of 5%～95% acetone solvent or three kinds of any ratios of solvent, 45～100 ℃, adopting frequency is 900～2500 megahertzes, power is under 500～15000 watts the microwave action, extract 2～7 times, each 15～90 minutes, merge extractive liquid,, the acetone that adds 10～70% times of amounts in the extracting solution, 0.05～5% crystallization auxiliary, left standstill 12～70 hours, separate out the mixed crystal of Carthamus yellow, promptly get Carthamus yellow, crystallization auxiliary is selected from organic base or alkaloids, as triethanolamine, aconitine, Ramulus Uncariae cum Uncis alkali, ligustrazine, caffeine, matrine, kopsine, ergotin and salt are as sodium citrate, sodium acetate, sodium bicarbonate, Disodium oxalate. etc.;
(2) preparation of safflower yellow A: following 4 kinds of any means all can obtain safflower yellow A, one, the macroporous resin of handling well on water-soluble or 0.1～15% ethanol of Carthamus yellow, with 5%, 15%, 30%, each 1～5 volume eluting of 45%, 60%, 75% and 90% ethanol, collect, merge 30% and 45% ethanol elution part, drying under reduced pressure promptly gets safflower yellow A; Its two, the sephadex lh-20 that balance is good on the water-soluble or methanol of Carthamus yellow, adopt water or methanol-water system (0: 100～100: 0) eluting, the component of collecting 1～5 column volume merges, drying under reduced pressure promptly gets safflower yellow A; Its three, good sephadex G-20, the water eluting of balance on the water-soluble or methanol of Carthamus yellow, the component of collecting 1～5 column volume merges, drying under reduced pressure promptly gets safflower yellow A; Its four, add 10%～30% ethyl acetate in the Carthamus yellow, 10%～30% acetone, 0.05～5% crystallization auxiliary left standstill 12～36 hours, separated out crystal, promptly got safflower yellow A.
5. according to any one described pharmaceutical composition of claim 1～4, it is characterized in that, described compositions can be prepared into the available dosage form on the various pharmaceuticss, as lyophilized injectable powder, tablet, drop pill, Sublingual tablet, dispersible tablet, capsule, granule, small-volume injection, bulk capacity injection.
6. according to any one described pharmaceutical composition of claim 5, it is characterized in that described compositions can preferred for preparation become small-volume injection.
7. treat obliterated cerebral vascular disease, stupor, paralysis and the hypophrenia that hepatic coma, hemiplegia, neurosurgery etc. cause, the application of memory disorder disease medicament aspect according to any one described pharmaceutical composition of claim 1～4 as preparation.
8. according to of the application of any one described pharmaceutical composition of claim 1～4 as preparation treatment coronary heart disease, vasculitis, post-stroke depression disease medicament aspect.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510109599 CN1762342A (en) | 2005-10-28 | 2005-10-28 | Safflor yellow A-containing pharmaceutical composition, its preparation method and usage |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510109599 CN1762342A (en) | 2005-10-28 | 2005-10-28 | Safflor yellow A-containing pharmaceutical composition, its preparation method and usage |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1762342A true CN1762342A (en) | 2006-04-26 |
Family
ID=36746801
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200510109599 Pending CN1762342A (en) | 2005-10-28 | 2005-10-28 | Safflor yellow A-containing pharmaceutical composition, its preparation method and usage |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1762342A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127009A (en) * | 2011-12-02 | 2013-06-05 | 浙江永宁药业股份有限公司 | Carthamin yellow sublingual tablet and preparation method and application thereof |
-
2005
- 2005-10-28 CN CN 200510109599 patent/CN1762342A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103127009A (en) * | 2011-12-02 | 2013-06-05 | 浙江永宁药业股份有限公司 | Carthamin yellow sublingual tablet and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN102716121B (en) | A kind of butylphthalide medicine active composition and preparation method thereof | |
| US20180071230A1 (en) | Formulations, salts and polymorphs of transnorsertraline and uses thereof | |
| CN1686458A (en) | Chinese medicinal composition, its preparation method and use | |
| CN1304039C (en) | Chinese medicine composition with functions of reducing blood-pressure, reducing-fat, anti-dizzy and calming wind, its preparing method and use | |
| CN101032503A (en) | Effective elements of Chinese traditional medicine combination for curing cardiovascular disease and the quality control method | |
| CN1843424A (en) | Cassia twig tuckahoe effervescence tablet and preparation method and its quality control method | |
| CN102340992B (en) | Pyrrolidine triple reuptake inhibitors | |
| CN1887283A (en) | Medicine composition containing bailobalide | |
| CN1915986A (en) | High purified tanshinone IIA sodium sulfonate, fabricating method, and preparation | |
| CN1768760A (en) | Medicinal composition containing safflower total flavone and its preparation process and usage | |
| CN1762342A (en) | Safflor yellow A-containing pharmaceutical composition, its preparation method and usage | |
| CN1857385A (en) | Medicine composition for treating cervical spondylosis and its preparing method | |
| CN1931212A (en) | Medicine for preventing and treating senile dementia and its prepn and use | |
| CN1887282A (en) | Medicine composition containing bailobalide | |
| CN1582952A (en) | Use of asiaticoside in preparation of medicines for diseases of cardio-cerebral blood vessels | |
| CN1059444C (en) | Composition for curing angicardiopathy and its production and usage | |
| JP2011246478A (en) | Solid dosage formulation of telcagepant potassium | |
| CN1636581A (en) | Safflower medicine composition and its prepn process and use | |
| CN1768740A (en) | Medicinal composition containing carthamin yellow and its preparation process and usage | |
| CN114917213B (en) | Mental disorder therapeutic agent comprising amitriptyline and method for treating mental disorder | |
| CN1251693C (en) | Chinese-western medicine compound preparation and its preparing method | |
| CN1751691A (en) | Small volume intravenous injection of gastrodine and its prepn. method | |
| CN1843343A (en) | Methocarbamol dispersion tablet | |
| CN1039198C (en) | Process for preparing diterpene alkaloid and its medicinal usage | |
| CN101045089A (en) | Traditional Chinese medicine with functions of tonifying-qi, supporting-Yang, tonifying-heart and clearing-damp, and its quality control method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C57 | Notification of unclear or unknown address | ||
| DD01 | Delivery of document by public notice |
Addressee: Xu Wenjie Document name: Deemed as a notice of withdrawal (Trial) |
|
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |