CN1895314A - A lyophilized powder for injection containing Notoginseng radix total saponin with good appearance and shatter resistance, and its preparation method - Google Patents
A lyophilized powder for injection containing Notoginseng radix total saponin with good appearance and shatter resistance, and its preparation method Download PDFInfo
- Publication number
- CN1895314A CN1895314A CN 200610010988 CN200610010988A CN1895314A CN 1895314 A CN1895314 A CN 1895314A CN 200610010988 CN200610010988 CN 200610010988 CN 200610010988 A CN200610010988 A CN 200610010988A CN 1895314 A CN1895314 A CN 1895314A
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- injection
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- radix notoginseng
- dried powder
- panax notoginseng
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- 235000003143 Panax notoginseng Nutrition 0.000 title claims abstract description 57
- 239000007924 injection Substances 0.000 title claims abstract description 50
- 238000002347 injection Methods 0.000 title claims abstract description 50
- 238000002360 preparation method Methods 0.000 title claims abstract description 19
- 229930182490 saponin Natural products 0.000 title abstract description 13
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- 239000000843 powder Substances 0.000 claims abstract description 70
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- 239000000047 product Substances 0.000 claims description 75
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The invention relates to a beautiful shatter-resistant panax notoginseng saponins freeze-dried powder injection and a preparation method thereof. The weight percentages of the effective components and the auxiliary materials of the medicine are as follows: total saponins of panax notoginseng: 95% -99.5%, mannitol: 0.5 to 5 percent, and is prepared by a certain method. Experiments show that the panax notoginseng saponins freeze-dried powder injection of the invention has the following advantages: the stability is good: the sample is placed for 2 years at normal temperature, the product is stable and reliable, and all indexes are qualified and completely meet the requirements; the effect of promoting blood circulation by removing blood stasis is stable and reliable: compared with the injection Xuesaitong, the medicine has better and more stable functions of promoting blood circulation and removing blood stasis, and better dissolution speed; the product has good appearance and is not easy to break; when in clinical use, a special solvent injection is not needed; the safety is better, and the method is particularly suitable for people allergic to alcohol; the pollution chance is reduced by 50 percent when the solvent is used compared with the special solvent injection; the use cost is reduced by 15-25% compared with the variety of the special solvent injection agent; can improve the dosage speed of nurses by 30 to 60 percent when in use.
Description
Technical field
The present invention relates to a kind of lyophilized injectable powder of forming with Radix Notoginseng total arasaponins and small amount of mannitol and the preparation method of product, this product is to have the biomedical product that has medical treatment or health care to be worth to blood circulation disease.
Background technology
Radix Notoginseng (having another name called Radix Notoginseng, Radix Notoginseng, southern Radix Ginseng) is the araliaceae ginseng plant, and its root, leaf, flower etc. all have medical value, mainly contain arasaponin (content is 2%～14%) and other material.Research data confirms that Radix Notoginseng total arasaponins is exactly the effective ingredient of pseudo-ginseng blood-circulation-invigovating silt, can effectively improve sanguimotor hemodynamics, blood viscosity lowering, and blood sugar lowering, blood fat prevent the comprehensive functions such as generation of vascular inflammation.Contained arasaponin belongs to ginsenoside's class, has found tens kinds of monomers such as Rg so far in the Radix Notoginseng
1, Rb
1, Panax Notoginseng saponin R
1, constant monomers such as Re, Rd, and micro-monomer and trace monomer Rh
1, Rh
2, Rf etc.Panax species is famous plant amedica, and the ginsenoside is its effective ingredient, and a large amount of both at home and abroad basic research, applied research, clinical research etc. all prove ginsenoside's prospect that is widely used.But, because cause such as other Radix Ginsengs (Radix Ginseng, Korean Ginseng, Radix Panacis Quinquefolii) price height and content of ginsenoside be low, have that the Radix Notoginseng price is low, content of ginsenoside is high only, thereby just have the value of commercial development preferably.The arasaponin product that extraction separation goes out from Radix Notoginseng at present has multiple, as Rg
1, Rb
1, Panax Notoginseng saponin R
1, Re, Rd etc., arasaponin, Radix Notoginseng total arasaponins, Radix Notoginseng extract etc.In these many products, have only Radix Notoginseng total arasaponins to have legal, disclosed quality standard, and most widely used, product relates to oral formulations, injection and some novel forms.Can obtain different arasaponins with different raw materials, different technology, or even the monomer arasaponin.Therefore, " arasaponin " made by the Radix Notoginseng total arasaponins extraction process of certain technological requirement (meets 1985 the earliest Yunnan Province or later 1996 version Yunnan Province standards and the Radix Notoginseng total arasaponins quality standard [" State Standard of the People's Republic of China WS3-B-3590-2001 (Z) (trying) "] of state approval now, the energy large-scale production, the product that circulation is arranged on the market just is called Radix Notoginseng total arasaponins.To be different from other arasaponin.The XUESAITONG general by name (as XUESAITONG ZHUSHEYE, panax notoginseng saponins for injection etc.) of Radix Notoginseng total arasaponins preparation and/or XUESHUANTONG (as injection XUESHUANTONG etc.).Also can be used in other the compound preparation.
The patent application of relevant arasaponin is more, " the arasaponin injectable powder and preparation method thereof " that publication number CN1491659A (application number 03139023.4) is arranged that relates to injection, its composition comprises Radix Notoginseng total arasaponins, excipient, Radix Notoginseng total arasaponins 5%～49.9%, surplus are excipient and moisture.Excipient is one or more a combination in any such as aminoacid, mannitol, lactose, glucose, PVP, low molecular dextran, sodium chloride, phosphate.The patent No. is the ZL patent No. 96101652.3 (publication number is CN1067244C), " a kind of arasaponin injectable powder ", form by arasaponin and water for injection dissolubility pharmaceutic adjuvant, the content of arasaponin is 50～99.5%, surplus is a pharmaceutic adjuvant, and pharmaceutic adjuvant is aminoacid, glucose, lactose, mannitol, PVP, low molecular dextran, sodium chloride, calcium gluconate or calcium phosphate.And the patent No. is ZL96107464.7 " a saponins powder for injecta solvent ".And the medicine that relates to the Radix Notoginseng total arasaponins preparation at present is less relatively.
Existing in the market XUESAITONG and XUESHUANTONG lyophilized injectable powder are pure notoginsen triterpenes freeze-dried powder pin, do not use the adjuvant of any interpolation, and it is higher, easily and the advantage of other product compatibilities that such product has purity.But product in the market (injection XUESHUANTONG and panax notoginseng saponins for injection etc.) appears at when moving frangible, mince and be bonded on bottle wall, make product appearance bad, the easier inferior sensation of product matter that causes, and then influence doctor and patient's psychology, we know that in the present clinical medicine idea, psychology also is one of extremely important factor.Because carrying is inevitably, and according to market demands and management expectancy, product must repeatedly be carried or move, and reaches safely in the user hands before the deadline to guarantee product.The frangible problem of product has so also become a major issue of product quality, also can cause harmful effect to user from psychological aspect simultaneously.Pure in addition saponin (present product) also occur dissolution velocity slow, must use the special-purpose solvent of annotating of alcoholic saponins injectable powder simultaneously, increase patient's expense simultaneously, increase nurse's dosing workload, increase in the use unfavorable factor such as opportunities for contamination.Especially now ethanol crowd hypersensitive is constantly increased, the risk of using existing XUESAITONG injectable powder is in continuous increase.From the clinical practice application point, the clinician must take dialectical executing to control to the patient that will give treatment to according to situations such as patient's disease time, the situation that is in a bad way, individual variations, the doctor will implement prescription power in the time of this, promptly the patient be implemented flexibly combination drug etc.Often will adjust prescription at any time according to situation in cardiovascular and cerebrovascular disease patient treatment process, the used medicine purity of prescription is higher in the time of this more helps the doctor and uses according to different situations.And the Radix Notoginseng total arasaponins injection is mainly used in this case, and clinically needs purer product.Therefore, product purity and easily be broken into a paradox.How to solve this contradiction, realize social benefit better, become a difficult problem.
Summary of the invention
Purpose of the present invention aims to provide a kind of reasonable recipe, comprehensive therapeutic effect is good, quality can be controlled attractive in appearance anti-crushing panax notoginseng saponins freeze-dried powder injection and its preparation method.
The present invention is directed to the problem that prior art exists,, invented new prescription through research and development in depth and to the follow-up study of the product that gone on the market, can this contradiction of fine solution.
Usually, solve the such problem of similar fragility, generally all be with more matrix type adjuvant, more macromolecular adjuvant, but we find under study for action, for example can be used as low molecular dextran that the injection adjuvant uses etc. with the Radix Notoginseng total arasaponins compatibility after occur in the injection greatest problem---clarity is defective, therefore, according to the character of this product, select one be fit to, an amount of adjuvant is a difficult problem.We find to add the mannitol of prescription total amount 0.5%～5% through after a large amount of basic research, can reach good mouldability, make every indexs such as product is non-friable, clarity good, can make product have better compatibility again, and convenient treatment is used.The product of gained is both artistic and practical.
In the acute ischemic cerebrovascular disease disease treatment, reduce intracranial pressure, treatment cerebral edema particular importance, promptly occur cerebral edema behind the cerebral infarction about 6 hours, and cerebral edema increases the weight of ischemia, the hypoxia response of local lesion, so should reach early treatment.Medicine commonly used is mannitol, glycerol, generally should give dehydrant 7～10.Research is proof also, and mannitol still has the effect that reduces platelet aggregation.
Panax notoginseng saponins freeze-dried powder injection of the present invention, the composition percentage by weight of effective ingredient and employed adjuvant is:
Radix Notoginseng total arasaponins 95%～99.5%
Mannitol 0.5%～5%
Every injectable powder is by Radix Notoginseng total arasaponins 100mg～800mg and mannitol 0.5mg～42mg, and moisture and unavoidable impurities composition.For example every Radix Notoginseng total arasaponins is that 100mg, mannitol are 0.5mg, and content total amount (loading amount) is about 100.6mg; Every Radix Notoginseng total arasaponins is that 800mg, mannitol are 42mg content total amount (loading amount) for about 842mg etc.
Preparation method is:
Under 10,000 grades condition, get the Radix Notoginseng total arasaponins raw material of qualified injection, it is dissolved in the water for injection with adjuvant, after activated carbon decolorizing is handled, add water for injection and be diluted to the cumulative volume amount, remove active carbon with quick filter paper filtering earlier, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the membrane filtration below the 0.2 μ m, fine straining liquid is sent into frozen vacuum dryer after sending into the racking machine packing, be chilled to subzero 36 ℃～39 ℃ fast, 2～5 hours, progressively slowly be warming up to 39 ℃～48 ℃ (needing 23 hours approximately), take out goods, Zha Gai, packing, check gets the lyophilized injectable powder finished product.
Produce the quality of used Radix Notoginseng total arasaponins raw material, reach outside the comprehensive Radix Notoginseng total arasaponins GB, also need to reach no abnormal toxicity, no thermal source, clarity is good, hemolytic is qualified, content is high.
Product of the present invention has the effect of good improvement and treatment blood circulation disease, is particularly useful for the first aid and the rehabilitation medication of cerebral ischemia and ischemic cardiovascular disease, and each drug dose that uses is: Radix Notoginseng total arasaponins: 100～1200mg.
Panax notoginseng saponins freeze-dried powder injection of the present invention our experiments show that:
One, good stability: sample was placed 2 years at normal temperatures, and product is reliable and stable, and every index is all qualified, meets the requirements fully;
Two, the effect ofactivating blood circulation to dissipate blood stasis is reliable and stable: product of the present invention compare with panax notoginseng saponins for injection have better, more stable function of promoting blood circulation to disperse blood clots;
Three, product appearance is good, and is non-friable.
Four, compare with existing XUESAITONG powder pin and have better dissolution velocity;
Five, during clinical use, do not need with the special-purpose solvent of annotating;
Six, safety is better, is particularly useful for the ethanol allergy sufferers;
Opportunities for contamination is than reducing by 50% with the special-purpose solvent of annotating when seven, using;
Eight, the cost that uses is than reducing by 15～25% with the special-purpose kind of annotating solvent;
Can improve nurse's the speed of making up a prescription 30%～60% when nine, using.
Product of the present invention has carried out study of pharmacy and part pharmacological research, and its result is as follows:
One, panax notoginseng saponins for injection stability of formulation
Sample with embodiment 1,2,3,4,5,6 at room temperature keeps in Dark Place, and places respectively 1,2,3,6,12,24 month, checks that on time outward appearance is constant substantially, and effective ingredient does not change through check yet.Therefore, the product that makes of the various prescriptions of this XUESAITONG lyophilized formulations all can reach the shelf-life in 2 years.
The stability test result: assay and discriminating etc. are with reference to existing GB WS-10986 (ZD-0986)-2002 in the quality standard.The result is as follows:
| Sample | Xiang Quanjian such as sample size, discriminating | |||||
| January | February | March | June | December | 24 months | |
| Example 1 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Example 2 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Example 3 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Example 4 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Example 5 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
| Example 6 | Qualified | Qualified | Qualified | Qualified | Qualified | Qualified |
The result shows sample provided by the invention, and through the preliminarily stabilised investigation, product quality is basicly stable, can reach more than 2 years.
Two, the function of promoting blood circulation to disperse blood clots of panax notoginseng saponins freeze-dried powder injection of the present invention and commercially available XUESAITONG powder pin is relatively:
1 experiment material
1.1 medicine and reagent
Adopt embodiment 1 injectable powder to do to compare sample for test agent (abbreviation agar) and commercially available XUESAITONG injectable powder (being called for short the powder pin).During test, it is made into 0.06g/ml, 0.03g/ml, 0.015g/ml and 0.0075g/ml concentration with 0.5%CMC-Na, for preventing to separate out, now with the current; The adrenalin hydrochloride injection; Carrageenin (Type 1, C1013), and Sigma company; ADP-2Na, the import packing; TT, PT, APTT and FIB measure test kit.
1.2 laboratory animal
Male SD rat, the cleaning level.
1.3 instrument
MCVS-2010 type cerebrovascular detection system, C2000-4 type high-performance magnetic bead method four-way coagulo meter and LBY-NS type four-way platelet aggregation instrument, LDZ-0.8 medical centrifuge.
1.4 statistical method
The normal distribution data are checked with t, and the skewness distributed data is checked with sum of ranks (u).
2 methods and result
2.1 influence to the formation of mice thrombus in vivo
70 of 20～22g Kunming mouses, male and female half and half are divided into 7 groups at random by sex and body weight: agar 0.1,0.2,0.4g/kg three dosage groups, positive control aspirin 100mg/kg group, XUESAITONG powder pin 0.2g/kg group, compound Salviae Miltiorrhizae 1.0g/kg group, the blank group, 10 every group.Each is organized all by 20ml/kg volume gastric infusion, once a day, and continuous 8 days.Irritated in 5th behind the stomach 30 minutes, each organizes the equal back of mice subcutaneous injection 1% carrageenin 40mg/kg, behind the 72h, observes afterbody thrombosis, measure afterbody total length and thrombosis length, calculate the percent of thrombosis length with afterbody thrombosis length divided by length overall.The results are shown in following table:
| Group | Dosage (/kg) | Number of animals (only) | Thrombosis length percent (X ± SD%) |
| 0.5％CMC-Na | 20ml | 10 | 37.34±24.18 |
| Aspirin | 100mg | 10 | 2.56±4.14 ** |
| The powder pin | 0.2g | 10 | 5.51±6.46 ** |
| FUFANG DANSHEN PIAN | 1.0g | 10 | 6.58±9.99 |
| Agar | 0.1g | 10 | 10.10±6.34 ** |
| 0.2g | 10 | 5.04±7.45 ** | |
| 0.4g | 10 | 2.52±4.59 ** |
Compare with the blank group: * P＜0.05, * * P＜0.01
Experimental result shows: the mouse tail thrombosis that product of the present invention and each positive controls on Carrageenan are brought out has remarkable inhibitory action.And the product of embodiment has good dose-effect relationship.Compare with commercially available injectable powder, the result shows that the freeze-dried powder of product of the present invention has better trend.
Three, notoginsen triterpenes freeze-dried powder pin is to the prevention and the therapeutical effect of cerebral ischemia
Reperfusion injury test behind pallasiomy transient ischemic attack and the ischemia
1, the observation of apoplexy index and mortality rate is calculated
Calculate apoplexy index in the pallasiomy cerebral ischemia reperfusion 6 hours with reference to the Ohno method, per hour observed and recorded once and calculates summation, observes and respectively organizes mortality rate in 24 hours.The freeze drying powder of Xuesaitong (this programme product is called for short agar) of XUESAITONG powder pin (commercially available, as to be called for short the powder pin), the embodiment of the invention 4.
| Group | n | The apoplexy index (x ± SD) | Mortality rate (%) |
| Blank | 30 | 19.23±3.10 | 33.3 |
| The powder pin | |||
| 80mg/kg | 15 | 10.11±2.70* | 0 |
| 40mg/kg | 15 | 12.94±2.10* | 6.6 |
| Agar | |||
| 80mg/kg | 15 | 9.18±2.97** | 0 |
| 40mg/kg | 15 | 12.70±2.12* | 4.7 |
With normal saline (blank group is relatively),
*P＜0.05,
*P＜0.01,
Comparatively speaking, product effect of the present invention is quite a lot of.
2, the Ca of brain cortical tissue
2+, Na
+And water content is measured
Get cortex of temporal lobe with reference to the Young method, handle the back atomic absorption spectrophotometer Ca of brain cortical tissue
2+, Na
+And water content, the result:
| Group | n | H 2O(％) | Ca 2+(μmol/g) | Na +(μmol/g) |
| Blank | 10 | 76.6±14.86 | 4.2071±0.8213 | 81.73±31.15 |
| The powder pin | ||||
| 80mg/kg | 10 | 74.3±1.31 | 2.0914±1.0172* | 67.20±14.00 |
| 40mg/kg | 10 | 74.7±0.96 | 1.9086±0.3814** | 69.8±7.22 |
| Agar | ||||
| 80mg/kg | 10 | 73.1±1.35 | 2.0902±1.0173* | 67.15±13.89 |
| 40mg/kg | 10 | 74.0±0.98 | 1.9079±0.3825** | 69.1±7.31 |
With normal saline (blank group is relatively),
*P＜0.05,
*P＜0.01
Compare with the commercially available prod, comparatively speaking, product effect of the present invention is quite a lot of.
Four, the safety testing of panax notoginseng saponins freeze-dried powder injection
Sample: the panax notoginseng saponins freeze-dried powder injection (agar) of commercially available XUESAITONG powder pin (powder pin), the embodiment of the invention 6
Test method: get 18～22g healthy mice, male and female half and half, tail vein iv gives powder pin or agar 0.4ml/10gtw respectively, observes 72 hours continuously after the administration, and test totally three times the results are shown in following table:
| Group | Number of animals | LD 50 |
| The powder pin | 20 | 291.9mg/kg |
| Agar | 20 | 298.4mg/kg |
The result shows: the basically identical as a result of mice oral XUESAITONG powder pin or freeze drying powder of Xuesaitong.
Five, irritation test
Get 4 of healthy rabbits, W:2.0～2.2kg, male and female half and half, be divided into two groups, respectively injection powder injection (with the special-purpose dissolution with solvents of annotating) or agar (with the sodium chloride for injection dissolving, embodiment 1) 1ml on its left and right sides lower limb quadriceps femoris, 48h puts to death rabbit behind the medicine, cut open the inspection quadriceps femoris, vertically cut and observe injection site muscular irritation reaction, and according to the form below converses corresponding order of reaction.
Local muscular irritation order of reaction table:
| Order of reaction | Irritant reaction |
| 0 | No significant change |
| 1 | Mild hyperaemia, its scope is less than 0.51.0cm |
| 2 | Moderate hyperemia, its scope is less than 0.51.0cm |
| 3 | Severe hyperemia is with myodegeneration |
| 4 | Necrosis occurs, the brown degeneration is arranged |
| 5 | The popularity necrosis appears |
The result:
The zest of commercially available XUESAITONG injectable powder is 5 grades, and the necrosis of popularity appears in injection site muscle, and showing has CR Critical zest.
Product zest of the present invention is 3 grades, and severe hyperemia appears in injection site muscle, with myodegeneration, shows that product has certain zest.
Comparatively speaking, the zest of product of the present invention is much smaller than the zest of commercially available prod.Reach one of main purpose of the present invention.
Six, product of the present invention is compared with existing notoginsen triterpenes freeze-dried powder pin and is had better anti-crushing property
Do anti-crushing Journal of Sex Research with product of the present invention (embodiment 1,6) and commercially available XUESAITONG powder pin, adopt mechanical sharp pounding method, time is in second (10s, 30s, 60s), (medicine is before using to shake the intensity that was equivalent to carry 25 times in 10 seconds, on average move number of times between 25～35 times), broken bottle number how much, and the percentage ratio in the bracket is percentage of damage.Statistical result such as following table:
| Group | Sample number | 10s | 30s | 60s |
| The powder pin | 20 | 20(100％) | Most of one-tenth powder | Whole powderings |
| Example 1 | 20 | 3(15％) | 7(36％) | 11(55％) |
| Example 6 | 20 | 0(0％) | 1(5％) | 3(25％) |
From The above results as seen, existing injectable powder, content (drug moiety) is broken nearly all before using, and causes product appearance very poor.Contain embodiment 1 sample of mannitol 0.5%, have only 15% percentage of damage, can reach substantially requirement (because of its degree of crushing relatively low), and contain embodiment 6 samples of mannitol 5%, occur broken.Therefore, we find that the mannitol content scope just can reach requirement 0.5% ~ 5%.
Seven, product of the present invention is compared with existing XUESAITONG powder pin and is had better dissolution velocity
Do dissolution velocity research with product of the present invention (embodiment 3) and commercially available XUESAITONG powder pin, all use water for injection, the result is as follows:
| Group | Sample number | Average dissolution time (s) |
| The powder pin | 10 | 45.5 |
| Agar | 10 | 21.3 |
Product dissolution velocity of the present invention improves more than 1 times, and reaches clinical required dissolution velocity (below 30 seconds).
Eight, during the clinical use of product of the present invention, do not need with the special-purpose solvent of annotating
As seven said, product water for injection of the present invention, or can both dissolving rapidly in 30 seconds with sodium chloride for injection or glucose for injection solution etc., need not use the alcoholic special-purpose solvent of annotating.
Nine, Product Safety of the present invention is better, is particularly useful for the ethanol allergy sufferers.
Contain the special use notes solvent of ethanol more than 35% owing to use in the existing XUESAITONG injectable powder clinical practice, blood vessel is had outside certain zest, still can not be applied to ethanol patient hypersensitive.And ethanol allergy is ignorant sometimes, therefore usually anaphylactoid danger can take place.As the clinical application product, safety guarantee is extremely important.Product of the present invention can be abandoned ethanol, improves security of products.
Opportunities for contamination was than reducing by 50% with the special-purpose solvent of annotating when ten, product of the present invention used.
Statistics and result of the test show, when dosing, a kind of solution of every increase (increase once allocate number of times) will increase the chance of pollution.With respect to using special-purpose secondary dosing of annotating the commercially available XUESAITONG powder pin of solvent, this product only needs a dosing to get final product, and opportunities for contamination was than reducing by 50% with the special-purpose solvent of annotating when corresponding product of the present invention used.
11, the cost of product use of the present invention is than the kind reduction by 15～25% with special-purpose notes solvent.
Because existing XUESAITONG powder pin product is and the supporting use of solvent is annotated in special use, the special-purpose cost of annotating solvent compare with injectable powder be about its 15 ~ 25%, therefore, will reduce by 15 ~ 25% without the cost of the product of the present invention of dedicated solvent.
Can improve nurse's the speed of making up a prescription 30%～60% when 12, product of the present invention uses.
Because existing XUESAITONG powder pin product is to annotate the supporting use of solvent with special use, uses special-purpose secondary dosing of annotating the commercially available XUESAITONG powder pin of solvent, the required time is more; Product of the present invention only needs a dosing to get final product, and the use of corresponding product of the present invention can improve nurse's the speed of making up a prescription 30%～60%.
The specific embodiment
Embodiment 1:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 100mg/ props up.
Raw material: Radix Notoginseng total arasaponins 100g (99.5%)
Mannitol 0.5g (0.5%)
Preparation method:
Under 10,000 grades condition, get the Radix Notoginseng total arasaponins raw material 100g of qualified injection, qualified medicine and adjuvant mannitol 0.5g are dissolved among the water for injection 800ml together, after activated carbon decolorizing (prior art) is handled, it is 1000ml that adding water for injection is diluted to cumulative volume, removes active carbon with quick filter paper filtering earlier, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m; Fine straining liquid is sent into racking machine, by every 1ml packing, covers the lid of trough of belt, sends into frozen vacuum dryer, is chilled to 35 ℃～40 ℃ fast, 2～3 hours, progressively slowly is warming up to 35 ℃～45 ℃ (needing 16 hours approximately); The jam-pack lid takes out goods, and Zha Gai, packing, check get qualified medicinal notoginsen triterpenes freeze-dried powder pin finished product.
Embodiment 2:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 150mg/ props up.
Raw material: Radix Notoginseng total arasaponins 150g (99.3%)
Mannitol 1g (0.7%)
Preparation method is substantially the same manner as Example 1.
Embodiment 3:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 250mg/ props up.
Raw material: Radix Notoginseng total arasaponins 250g (96.2%)
Mannitol 10g (3.8%)
Preparation method is substantially the same manner as Example 1.
Embodiment 4:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 400mg/ props up.
Raw material: Radix Notoginseng total arasaponins 400g (95.2%)
Mannitol 20g (4.8%)
Preparation method:
Under 10,000 grades condition, get the Radix Notoginseng total arasaponins raw material 400g of qualified injection, qualified medicine and adjuvant are dissolved among the water for injection 3200ml together, after activated carbon decolorizing was handled, it was 4000ml that adding water for injection is diluted to cumulative volume.Earlier remove active carbon, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m with quick filter paper filtering; Fine straining liquid is sent into racking machine, by every 4ml packing, covers the lid of trough of belt, sends into frozen vacuum dryer, is chilled to 35 ℃～38 ℃ fast, 2～3 hours, progressively slowly is warming up to 35 ℃～45 ℃ (needing 21 hours approximately); The jam-pack lid takes out goods, and Zha Gai, packing, check get qualified medicinal notoginsen triterpenes freeze-dried powder pin finished product.
Embodiment 5:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 600mg/ props up.
Raw material: Radix Notoginseng total arasaponins 600g (97.1%)
Mannitol 18g (2.9%)
Preparation method is substantially the same manner as Example 4.
Embodiment 6:
Produce 1000 panax notoginseng saponins freeze-dried powder injections, product specification: 800mg/ props up.
Raw material: Radix Notoginseng total arasaponins 800g (95.0%)
Mannitol 42g (5.0%)
Preparation method:
Under 10,000 grades condition, get the Radix Notoginseng total arasaponins raw material 800g of qualified injection, qualified medicine and adjuvant are dissolved among the water for injection 6400ml together, after activated carbon decolorizing is handled, add water for injection and be diluted to 8000ml; Earlier remove active carbon, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m with quick filter paper filtering; Fine straining liquid is sent into racking machine, by every 8ml packing, covers the lid of trough of belt, sends into frozen vacuum dryer, is chilled to 35 ℃～37 ℃ fast, 2～3 hours, progressively slowly is warming up to 35 ℃～46 ℃ (needing 29 hours approximately).The jam-pack lid takes out goods, and Zha Gai, packing, check get qualified medicinal notoginsen triterpenes freeze-dried powder pin finished product.
Above embodiment is only for the present invention is described further, and scope of the present invention be not subjected to lift
The limitation of embodiment.
The definition of relevant material name or explanation:
Rg
1, Rb
1, Rd, Re etc. are a kind of monomers in the dammarane type that extraction separation goes out in the panax species (dammarane) saponin.
Panax Notoginseng saponin R
1: be a kind of monomer in the distinctive dammarane type of Radix Notoginseng (dammarane) saponin that extraction separation goes out in the Radix Notoginseng.
Arasaponin: refer to the general name of dammarane type (dammarane) saponin that goes out by extraction separation in the Radix Notoginseng, can be monomer, also can be mixture, comprise Radix Notoginseng total arasaponins.
Radix Notoginseng total arasaponins: refer to a kind of by the drug standard that meets country promulgation that goes out by specific production technology extraction separation in the Radix Notoginseng to contain Rg
1, Rb
1, Panax Notoginseng saponin R
1, Rd, Re saponin be main ginsenoside's effective site.Material name is a Radix Notoginseng total arasaponins, and the preparation name is called 'Xuesaitong ' formulation or Xueshuantong preparation, as XUESAITONG ZHUSHEYE, panax notoginseng saponins for injection, injection XUESHUANTONG etc.
Radix Notoginseng extract: be meant the extract that contains compositions such as arasaponin, polysaccharide that goes out by extraction separation in the Radix Notoginseng, be a kind of primary extract.
Radix Notoginseng total arasaponins product: comprise that XUESAITONG and XUESHUANTONG etc. are the various medicines of main active with the Radix Notoginseng total arasaponins.
Moisture is meant the moisture that can not eliminate fully for various reasons in the freeze-dried powder, generally between 0.1%～10%.
Unavoidable impurities: do not have absolute pure material in the world.Inevitably material is meant by supplementary material or the impurity brought into by the course of processing.But these impurity reach standard-required by medicine relevant requirements and pharmacopeia or standard test.The impurity of checking as the related substance item, heavy metal etc.
Claims (3)
1, a kind of anti-crushing panax notoginseng saponins freeze-dried powder injection attractive in appearance is characterized in that the composition percentage by weight of effective ingredient and adjuvant is:
Radix Notoginseng total arasaponins: 95%～99.5%
Mannitol: 0.5%～5%.
2, anti-crushing panax notoginseng saponins freeze-dried powder injection attractive in appearance according to claim 1 is characterized in that every product by Radix Notoginseng total arasaponins 100mg～800mg and mannitol 0.5mg～42mg, and moisture and unavoidable impurities composition.
3, the preparation method of the described panax notoginseng saponins freeze-dried powder injection of claim 1, it is characterized in that: under 10,000 grades condition, get the Radix Notoginseng total arasaponins raw material of qualified injection, it is dissolved in the water for injection with adjuvant, after activated carbon decolorizing is handled, add water for injection and be diluted to the cumulative volume amount, earlier remove active carbon with quick filter paper filtering, after the processing such as filter membrane coarse filtration of filtrate through filter paper and 0.4 μ m, under 100 grades condition, with the following membrane filtration of 0.2 μ m, after fine straining liquid is sent into the racking machine packing, send into frozen vacuum dryer, be chilled to subzero-36 ℃～-39 ℃ fast, 2～5 hours, progressively slowly be warming up to 39 ℃～48 ℃ (needing 23 hours approximately), take out goods, Zha Gai, packing, check gets the lyophilized injectable powder finished product.
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|---|---|---|---|
| CNB2006100109885A CN100484517C (en) | 2006-06-28 | 2006-06-28 | A lyophilized powder for injection containing Notoginseng radix total saponin with good appearance and shatter resistance, and its preparation method |
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|---|---|---|---|
| CNB2006100109885A CN100484517C (en) | 2006-06-28 | 2006-06-28 | A lyophilized powder for injection containing Notoginseng radix total saponin with good appearance and shatter resistance, and its preparation method |
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Cited By (2)
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|---|---|---|---|---|
| CN102512466A (en) * | 2011-12-27 | 2012-06-27 | 广西梧州制药（集团）股份有限公司 | Panax notoginseng saponins freeze-dried powder injection and preparation method thereof |
| US11351184B2 (en) * | 2017-07-07 | 2022-06-07 | Qi Liu | Preparation of Pulsatilla saponin B4 for injection |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1067244C (en) * | 1996-02-17 | 2001-06-20 | 昆明制药股份有限公司 | Notoginsenoside powder injection |
-
2006
- 2006-06-28 CN CNB2006100109885A patent/CN100484517C/en active Active
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102512466A (en) * | 2011-12-27 | 2012-06-27 | 广西梧州制药（集团）股份有限公司 | Panax notoginseng saponins freeze-dried powder injection and preparation method thereof |
| US11351184B2 (en) * | 2017-07-07 | 2022-06-07 | Qi Liu | Preparation of Pulsatilla saponin B4 for injection |
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| CN100484517C (en) | 2009-05-06 |
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