CN1799585A - Intravenous administered formulation of spreading hedyotis herb and its preparation method - Google Patents
Intravenous administered formulation of spreading hedyotis herb and its preparation method Download PDFInfo
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Abstract
The invention provides an injection of oldenlandia for venous administration and its preparing process, which integrates the techniques of freeze-dried powder injection and venous route of administration, the effective portions of the oldenlandia is extracted, and the impurity constituents in the oldenlandia are removed.
Description
Technical field
The present invention relates to a kind of intravenous administered formulation of spreading hedyotis herb and preparation method thereof.
Background technology
Herba Hedyotidis Diffusae is China's Chinese medicine, is the dry or fresh herb of genus rubia section plant Herba Hedyotidis Diffusae (Hedyotis diffusa willd.).Nature and flavor are sweet, light, cool, have the function of heat-clearing and toxic substances removing, promoting diuresis to eliminate damp pathogen, activating blood circulation to dissipate blood stasis, reducing swelling and alleviating pain.Be widely used in the treatment that the swollen Serpentis of heat syndrome, gastroenteropathy, tumor, urologic disease, skin ulcer stings etc.Modern pharmacological research shows that Herba Hedyotidis Diffusae mainly has enhance immunity activity and anti-tumor activity, has hepatic cholagogic, antibiotic, calm, hypnosis, analgesia, the growth of inhibition sperm in addition, regulates effect such as gastrointestinal function.Clinically, Herba Hedyotidis Diffusae can be used for treating various cancers, and especially alimentary tract cancer and lymphsystem tumor are as gastric cancer, the esophageal carcinoma, rectal cancer, malignant lymphoma, pulmonary carcinoma, cervical cancer, ovarian cancer, bladder cancer etc.; Also can be used for treating appendicitis, chronic colitis, acute and chronic nephritis, hepatitis, gastritis, respiratory tract infection and cutaneous diseases etc.Herba Hedyotidis Diffusae is widely used, determined curative effect, and toxic and side effects is low, and aboundresources.At present the single usefulness of this product has only water decoction and intramuscular injection aqueous injection, and both all have the serious limit that lacks, and have limited its application.
Summary of the invention
The invention discloses freeze-dried powder preparation of a kind of evident in efficacy and stay-in-grade injection Herba Hedyotidis Diffusae and preparation method thereof.
The invention also discloses a kind of evident in efficacy and stay-in-grade intravenous BAIHUASHESHECAO ZHUSHEYE preparation and preparation method thereof.
The invention also discloses a kind of Herba Hedyotidis Diffusae sodium chloride of evident in efficacy and stay-in-grade intravenous drip or glucose injection formulation and preparation method thereof.
Freeze-dried powder of the present invention and injection dosage form can improve stability of drug, avoid intermediate link, and be quality controllable, more safe and effective and be convenient to the transportation with the storage.
Instillation of the present invention meets the requirements with the injection dosage form stability, avoids intermediate link, and is quality controllable, reduces the cross-contamination probability, more safe and effective and easy to use.
Technical scheme of the present invention is as follows:
A kind of formulation of spreading hedyotis herb is characterized in that each raw material and excipient component thereof make freeze dried powder in following ratio:
(1), Herba Hedyotidis Diffusae 1500-2500g
(2), excipient is following a kind of composition or multiple mixture of ingredients: mannitol, mannitol lactose, glucose dextran, gelatin hydrolysate are 50-150g
(3), sodium sulfite 1-3g
(4), sterile water for injection adds to 2000ml.A kind of formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous fluid in following ratio:
(1), Herba Hedyotidis Diffusae 1500-2500g
(2), chlorobutanol 0.5-1.5g or polyoxyethylene sorbitan monoleate 15-25g, the two selects one,
(3), sodium sulfite 1-3g
(4), sterile water for injection adds to 2000ml.A kind of formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous drip liquid in following ratio:
(1), Herba Hedyotidis Diffusae 20-200g
(2), sodium chloride 9g
(3), sodium sulfite 250mg
(4), sterile water for injection adds to 1000ml.A kind of formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous drip liquid in following ratio:
(1), Herba Hedyotidis Diffusae 20-200g
(2), glucose 50g
(3), sodium sulfite 500mg
(4), sterile water for injection adds to 1000ml.Described formulation of spreading hedyotis herb (freeze dried powder) is characterized in that each raw material components proportioning is:
(1), Herba Hedyotidis Diffusae 2000.0g
(2), excipient is following a kind of composition or multiple mixture of ingredients: mannitol, mannitol lactose, glucose dextran, gelatin hydrolysate are 100.0g
(3), sodium sulfite 2g
(4), sterile water for injection adds to 2000.0ml.Described formulation of spreading hedyotis herb (intravenous fluid) is characterized in that each raw material components proportioning is:
(1), Herba Hedyotidis Diffusae 2000.0g
(2), chlorobutanol 1g or polyoxyethylene sorbitan monoleate 20g, select one in two components,
(3), sodium sulfite 2g
(4), sterile water for injection adds to 2000.0ml.Described formulation of spreading hedyotis herb (intravenous drip liquid) is characterized in that each raw material components proportioning is:
(1), Herba Hedyotidis Diffusae 100.0g
(2), sodium chloride 9g
(3), sodium sulfite 250mg
(4), sterile water for injection adds to the described formulation of spreading hedyotis herb of 1000ml (intravenous drip liquid), it is characterized in that each raw material components proportioning is:
(1), Herba Hedyotidis Diffusae 100.0g
(2), glucose 50g
(3), sodium sulfite 500mg
(4), sterile water for injection adds to 1000ml
The preparation method of described formulation of spreading hedyotis herb (freeze dried powder) is characterized in that may further comprise the steps: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", is cut into the 2-3cm section, add alcohol reflux, filtrate decompression backflow ethanol also concentrates, and adds the neutral water stirring and dissolving, leaves standstill, incline and upper strata liquid, centrifugal, be heated to 40-80 ℃, be added on and handle well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, backflow ethanol, add the neutral water heating for dissolving again, dilution is heated to 40-80 ℃, filter while hot, be added on and handle well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, decompression recycling ethanol adds water to 1000ml to 400ml-500ml, adds proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulates pH value 6.5-7.0 with sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content, filter through the microporous filter membrane terminal again, be sub-packed in the sodium calcium control injection bottle of 10ml every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
Above-mentioned preparation method, it is characterized in that: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add the 65-85% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add the 65-85% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 65-85% ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative (get 100ml put water bath method after residue detect), collect alcohol eluen, decompression recycling ethanol is to 500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content filters through 0.22 μ m microporous filter membrane terminal after pH is qualified again, be sub-packed in the sodium calcium control injection bottle of 10ml, every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
Above-mentioned preparation method, it is characterized in that: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 80% ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative (get 100ml put water bath method after residue detect), collect alcohol eluen, decompression recycling ethanol is to 500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content filters through 0.22 μ m microporous filter membrane terminal after pH is qualified again, in the sodium calcium control injection bottle of packing 10ml, every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
The preparation method of described formulation of spreading hedyotis herb (intravenous fluid) is characterized in that may further comprise the steps: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", is cut into the 2-3cm section, add alcohol reflux, filtrate decompression backflow ethanol also concentrates, and adds the neutral water stirring and dissolving, leaves standstill, incline and upper strata liquid, centrifugal, be heated to 40-80 ℃, be added on and handle well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, backflow ethanol, add the neutral water heating for dissolving again, dilution is heated to 40-80 ℃, filter while hot, be added on and handle well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, decompression recycling ethanol is to 400ml-500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds chlorobutanol or polyoxyethylene sorbitan monoleate, regulates pH value 6.5-7.0 with sodium hydroxide solution, adds sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content, filter through the microporous filter membrane terminal again, embedding is in 2ml or the brown injection bottle of 5ml, and sterilization gets final product.
The preparation method of described formulation of spreading hedyotis herb (intravenous drip liquid), the check that it is characterized in that learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50 60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol is to crude drug volume ratio 2: 1, and thin up (if insoluble matter is arranged, adds 10% sodium hydroxide solution and regulates pH value and make it dissolving to crude drug volume ratio 1: 3-5, but pH value is no more than 7.0), the active carbon that adds 0.1% (g/ml), heated and boiled 15～30 minutes filters, filtrate for later use is measured intermediate content.Take by weighing the sodium chloride of recipe quantity, be dissolved in the water for injection of 90 ℃ of 250-500ml, stirring is dissolved sodium chloride fully, add 0.1% active carbon, insulated and stirred 15 minutes, filtering decarbonization, and regulate in pH value to 5.5～6.5 scopes, measure content, merge, regulate pH value to 6.0～7.0 with 10% sodium chloride solution with above-mentioned Herba Hedyotidis Diffusae filtrate, the active carbon that adds 0.05% (g/ml) after boiling, kept fluidized state 15～30 minutes, and filtered, add the injection water to 900ml, add sodium sulfite,, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, play filter, the embedding branch is filled in 100ml or the 250ml infusion bottle, sterilization, promptly get or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, promptly.
The preparation method of described formulation of spreading hedyotis herb (intravenous drip liquid), the check that it is characterized in that learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol was to crude drug volume ratio 2: 1, thin up adds the active carbon of 0.1% (g/ml) to crude drug volume ratio 1: 3-5 (if insoluble matter is arranged, add 10% sodium hydroxide solution adjusting pH value and make it dissolving, but pH value is no more than 7.0), heated and boiled 15～30 minutes, filter, filtrate for later use is measured intermediate content.Take by weighing the glucose of recipe quantity, be added in the water for injection that boils, make into the concentrated solution of 50%-60%, it is an amount of to add hydrochloric acid, adds 0.1% active carbon heated and boiled simultaneously 15～30 minutes, filtering decarbonization, measure content, merge, regulate pH value to 6.0～7.0 with 10% sodium chloride solution with above-mentioned Herba Hedyotidis Diffusae filtrate, the active carbon that adds 0.05% (g/ml) after boiling, kept fluidized state 15-30 minute, and filtered, add the injection water to 500ml, add sodium sulfite,, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, ultrafiltration divides to be filled in 100ml or the 250ml infusion bottle, sterilization, promptly; Or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, sterilization, promptly.
Modern pharmacology research
Herba Hedyotidis Diffusae is the whole herb with root of Maguireothamnus speciosus Herba Hedyotidis Diffusae, the effect that heat clearing away, dampness removing, detoxifcation are arranged, control dyspnea and cough due to lung-heat. tonsillitis, pharyngolaryngitis, appendicitis, dysentery, jaundice, pelvic inflammatory disease, adnexitis, carbuncle furuncle, venom etc. are Chinese herbal medicine commonly used.Pharmacological research shows that Herba Hedyotidis Diffusae has antitumor, antibiotic, antiinflammatory isoreactivity.Herba Hedyotidis Diffusae has faint antibacterial action.Experiment showed, that this product can improve the phagocytic function of reticuloendothelial system, can stimulate reticuloendothelial cell hyperplasia, strengthen cytophagous vigor, so show as stronger anti-infectious function.As can be seen, Herba Hedyotidis Diffusae can stimulate the generation of mouse antibodies from experiment, and the antibody-secreting amount is increased, and lymphopoiesis is had obvious facilitation.
Pharmacodynamic study
According to herbal medicine efficacy research guideline, one of pharmacodynamic index for the treatment of this medicine should be to have antiinflammatory, immunomodulating and in-vitro antibacterial.The main pharmacodynamics research experiment of injection Herba Hedyotidis Diffusae adopts splenocyte increment and antibody forming cell's test, observes the immunization of injection Herba Hedyotidis Diffusae; The antibacterial action of adopt in the body, the in-vitro antibacterial method being observed the injection Herba Hedyotidis Diffusae.The injection Herba Hedyotidis Diffusae all has the obvious suppression effect to mice ear and rat granulation hyperplasia as a result; The effect that promotes splenocyte increment and antibody forming cell is arranged; Antibacterial experiment shows that it has certain vitro antibacterial activity, abnormal response do not occur in the intravenously administrable process.Conclusion: injection Herba Hedyotidis Diffusae and intravenous route administration have obvious anti-inflammatory and anti, immunomodulating and vitro antibacterial activity.
1. injection Herba Hedyotidis Diffusae (BH) is to the influence of mice ear
Get 50 of mices, body weight 18～22g, ♀ ♂ half and half is divided into 5 groups at random, 10 every group.Be matched group, BAIHUASHESHECAO ZHUSHEYE group (for three days on end, 30min begins experiment after the d3 administration for 1.2g/kg, im administration), BH (0.6,1.2,2.4g/kg) group, the BHiv administration, for three days on end, 10min begins test after the administration of d3 tail vein injection.Be coated with 100% dimethylbenzene 0.05ml on ear two sides, a mice left side, auris dextra compares, and puts to death mice behind the 1h, cuts two ears along the auricle baseline, prepares the mice auricle with 9mm diameter card punch, uses scales/electronic balance weighing, is swelling degree (inflammation index) with the difference of two ear weight.BH (0.6,1.2.2.4g/kg) the inductive mice ear degree of iv3d xylol has the obvious suppression effect.See Table 1.
The influence of the inductive mice ear degree of table 1 BH xylol (n=10, X ± s)
| Group | Dosage (g/kg) | Ear swelling degree (mg) |
| Matched group Herba Hedyotidis Diffusae (im) BH (iv) | - 1.2 0.6 1.2 2.4 | 23.52±5.66 18.17±3.87′ 18.01±4.21′ 17.05±4.99′ 16.29±4.49″ |
Compare with matched group: ' ρ＜0.05, " ρ＜0.01.
2.BH cotton balls is induced the granulomatous influence of rat
Get 40 of SD rats, body weight 150～180g, ♂.Etherization, fixing, abdominal incision, with two sterilization cotton balls (every weight (50 ± 1) mg, autoclaving), it is subcutaneous to implant rat both sides groin respectively.Operation administration on the same day, rat is divided into 5 groups at random, 8 every group; Be matched group, BAIHUASHESHECAO ZHUSHEYE group (1.0g/kg, the im administration, continuous 7 days, 30min begins experiment after the d7 administration), BH (0.5,1.0,2.0g/kg) group, BHiv administration, continuous 7 days, 10min puts to death rat after the d7 administration, take out cotton balls, after 60 ℃ of baking boxs are placed 12h, claim to deduct its dry weight the raw cotton ball weight and be the granuloma net weight.Table 2 is the result show, BH (0.5,1.0,2.0g/kg) has the obvious suppression effect to the rat granuloma hypertrophy.
Table 2 BH to the swollen outgrowth influence of rat cotton balls meat (X ± s, n=8)
| Group | Dosage (g/kg) | Swelling degree (Δ mg) | Suppression ratio (%) |
| Contrast Herba Hedyotidis Diffusae (im) BH (iv) | - 1.0 0.5 1.0 2.0 | 8 7.04±7.35 77.53±8.6* 79.11±5.91* 71.01±9.60* 66.14±7.07** | - 10.93 9.11 18.42 23.91 |
Compare with matched group: * P＜0.05, * * P＜0.01
3.BH to effect of immunologic function
(1) 60 of BALB/C mice, ♀ ♂ half and half, body weight 19～22g are got in the splenocyte breeder reaction.Be divided into 6 groups at random, 10 every group, i.e. matched group, model group, BAIHUASHESHECAO ZHUSHEYE group (30min begins experiment after the d7 administration for 1.2g/kg, im administration), BH (0.6,1.2,2.4g/kg) group.BHip administration, 7d continuously.Test preceding 2d and rise, except that matched group, each organizes the equal sc cyclophosphamide of mice 80mg/kg once.10min after the last administration puts to death each group mice dislocation, puts 75% alcohol-pickled 5min, under aseptic condition, take out spleen, remove tunicle, use Hank ' s liquid to wash 2 times, shred, piece of tissue is put into micro glass homogenizer, grind repeatedly, make splenocyte suspension, with 200 order net filtration splenocytes, carry out cell counting then, be made into 5 * 10
6/ ml is stand-by.
Improve to experimentize by the Mosmann method slightly, the cell suspension of adjusting is joined in the 96 porocyte culture plates, establish 8 holes, multiple hole for every group, every hole 200 μ l (5 * 10
6/ ml), add final concentration 10 μ g/ml ConA or 20 μ g/mlLPS to every hole then, put 37 ℃ of 5%CO
2Incubator was cultivated 66 hours, took out culture plate, and every hole adds 5mg/ml MTT 20 μ l, continued to cultivate 4～6 hours.Take out Sptting plate, centrifugal 3000r/min 10min inhales and abandons supernatant, and every hole adds acidify isopropyl alcohol 150 μ l, and in agitator vibration 30 seconds, fully mixing read the A value at microplate reader 570nm place behind the 10min.Table 3 is the result show, BH (0.6,1.2,2.4g/kg) is in the effect that promotes splenocyte propagation.
Table 3 BH to the influence of mouse boosting cell breeder reaction (X ± s, n=10)
| Group | Dosage (g/kg) | A value (570nm) | |
| ConA | LPS | ||
| Contrast model Herba Hedyotidis Diffusae (im) BH (iv) | - - 1.2 0.6 1.2 2.4 | 1.284±0.149** 0.763±0.130 0.946±0.133** 0.892±0.103* 0.981±0.128** 1.081±0.171** | 1.316±0.131** 0.836±0.148 1.080±0.106** 0.980±0.099* 1.050±0.122** 1.139±0.154** |
Compare with matched group: * P＜0.05, * * P＜0.01
(2) antibody forming cell measures grouping and medication same " splenocyte breeder reaction ", and from testing preceding 2d, except that matched group, each organizes the equal sc cyclophosphamide of mice 80mg/kg once; From testing preceding 2d, each SRBC 0.2ml/ that organizes ip in mice 10% only.10min after the last administration puts to death each group mice dislocation, takes out spleen and prepares individual cells, with containing Ca
2+, Mg
2+Ionic PBS furnishing 1 * 10
7Individual/ml.
The extracting spleen cell suspension is a medium with the PBS of pH7.2, in small test tube, adds above-mentioned splenocyte suspension 1ml, adds 0.2%SRBC 1ml and fresh guinea pig serum (1: 20) diluent 1ml, and fully mixing is put 37 ℃ of incubation 1h.The experimental port cumulative volume is 3ml.Establish cell negative control, complement control, SRBC contrast and PBS blank (zeroing is used) simultaneously.It is centrifugal that (2000r/min 10min), gets supernatant 2ml, puts visible spectrophotometer and measures its light absorption value (A), detects wavelength 413nm.Table 4 is the result show, BH (1.2,2.4g/kg) has enhancing antibody to form the effect of cell.
Table 4 BH to mouse boosting cell antibody forming cell's influence (X ± s, n=10)
| Group | Dosage (g/kg) | A value (413nm) |
| Contrast model Herba Hedyotidis Diffusae (im) BH (iv) | - - 1.2 0.6 1.2 2.4 | 1.102±0.107** 0.826±0.123 0.964±0.132* 0.888±0.125 1.004±0.222* 1.006±0.147** |
Compare with matched group: * P＜0.05, * * P＜0.01
4. vitro antibacterial activity
(1) preparation of antibacterial bacterial concentration is gone down to posterity 3-4 after generation repeatedly with various bacteria resuscitation, gets quantitative meat soup inoculation bacterium liquid and cultivates 6h at 37 ℃, regulates bacterial concentration and reaches 0.5 Maxwell than cloud point, and promptly bacterial concentration 107CFU/ml is stand-by.Every kind of antibacterial of the mensuration of MIC is established 9 dilution factors, and each dilution factor is established 3 multiple pipes, and the 10th hole contrasts as antibacterial simultaneously.Contain crude drug 4g/ml with the MH culture fluid being subjected to reagent to transfer to every milliliter earlier, then with this medicinal MH culture fluid culture fluid of 4g/ml doubly doubly dilution be 2,1,0.5,0.25......0.00802g/ml, place test tube (1ml/ pipe) respectively, every pipe adds the 0.1ml107CFU/ml antibacterial, after in 37 ℃ of constant incubators, cultivating 24h, observation has or not bacterial growth, determines the minimum inhibitory concentration (MIC) that antibacterial does not grow, and record MIC value.
Table 5 is the result show, at external BH 8 kinds of used antibacterials of experiment all had in various degree bacteriostasis.(2) MBC measures and adopts meat soup doubling dilution viable bacteria counting method, promptly in the drug solution of doubling dilution, add certain density bacterium liquid, behind the mixing in 37 ℃ of constant temperature culture 24h, measure the MIC value earlier, that will not see bacterial growth more successively respectively manages respectively sucking-off 0.1ml of culture fluid, carry out dull and stereotyped count plate, wherein clump count is no less than 5 dull and stereotyped pairing lowest concentration of drug, is the MBC value of this medicine.
Table 5 is the result show, external, BH has in various degree bactericidal action to 8 kinds of used antibacterials of experiment.
Table 5BH is to the mensuration of minimum inhibitory concentration and the minimum bactericidal concentration of antibacterial
| Antibacterial | The strain number | MIC(g/ml) | MBC(g/ml) |
| Staphylococcus aureus MRSE beta hemolytic streptococcus micrococcus catarrhalis Escherichia coli typhoid bacillus staphylococcus aureuses (ATCC25923) Escherichia coli (ATCC35218) | 1 1 1 1 1 1 1 1 | 2.0 4.0 4.0 4.0 4.0 4.0 2.0 4.0 | 4.0 4.0 4.0 4.0 ＞4.0 ＞4.0 ＞4.0 ＞4.0 |
5. vivo bacteria corrosion action
(1) 100 of mices is got in the influence of golden Portugal bacterium infecting mouse, body weight 18～20g, ♀ ♂ half and half, it is divided into 5 groups at random, every group 20, i.e. matched group, BAIHUASHESHECAO ZHUSHEYE (1.2g/kg, im administration, continuously and, 30min begins experiment after the d3 administration) group, BH (0.6,1.2,2.4g/kg) group.The BHiv administration, for three days on end, 10min after the administration of d3 tail vein injection, mouse peritoneal injection staphylococcus aureus (1 * 10
9Individual/ml) 0.5ml, whether observe the general situations of mices in 2 weeks and death then.Table 6 is the result show, BH does not have obvious protective effect to golden Portugal bacterium mice infected.
Table 6BH is to the influence of golden Fructus Vitis viniferae infecting mouse
| Group | Dosage (g/kg) | Bacterial concentration (individual/ml) | Number of animals | Gold Portugal bacterium | |
| Death toll | Mortality rate (%) | ||||
| Contrast Herba Hedyotidis Diffusae (im) BH (iv) | - 1.2 0.6 1.2 2.4 | 1×10 9 1×10 9 1×10 9 1×10 9 1×10 9 | 20 20 20 20 20 | 20 19 20 18 19 | 100 95 100 90 95 |
(2) 100 of mices are got in the influence of Bacillus typhi infecting mouse, body weight 18～20g, male and female half and half, it is divided into 5 groups at random, every group 20, i.e. matched group, BAIHUASHESHECAO ZHUSHEYE group (1.2g/kg, im administration, for three days on end, 30min begins experiment after the d3 administration), BH (0.6,1.2,2.4g/kg).The Bhiv administration, for three days on end, 10min after the d3 administration, mouse peritoneal injection Bacillus typhi (whether 1 * 109/ml) 0.5ml observed the general situations of mices in 2 weeks and death then.Table 7 is the result show, BH does not have obvious protective effect to the Bacillus typhi mice infected.
Table 7BH is to the influence of Bacillus typhi infecting mouse
| Group | Dosage (g/kg) | Bacterial concentration (individual/ml) | Number of animals | Bacillus typhi | |
| Death toll | Mortality rate (%) | ||||
| Contrast Herba Hedyotidis Diffusae (im) BH (iv) | - 1.2 0.6 1.2 2.4 | 1×10 9 1×10 9 1×10 9 1×10 9 1×10 9 | 20 20 20 20 20 | 19 17 18 19 18 | 95 85 90 95 90 |
Acute toxinology experiment
Entrust the test of pharmacology teaching and research room of Medical University Of Anhui, the result shows: mice iv administration, and injection Herba Hedyotidis Diffusae maximum tolerated dose is 160g/kg; The ip in mice administration, injection Herba Hedyotidis Diffusae maximum tolerated dose is 160g/kg.
(" Chinese medicine voluminous dictionary " carries, this product LD
50Be mice chamber injection crude drug 104g/ kg body weight.)
Clinical research
1. treat multiple cancer: use medicine compatibilities such as Herba Hedyotidis Diffusae, Rhizoma Imperatae and treat gastric cancer 81 examples altogether, 15 examples of fully recovering, produce effects 7 examples, effective 30 examples, total effective rate 75.30%; Single with Herba Hedyotidis Diffusae, Herba Houttuyniae, etc. the medicine compatibility side of one-tenthing or cooperation radiotherapy or chemotherapeutic treatment pulmonary carcinoma 33 examples, result's person's 24 examples more than 1 year of surviving; With in treatment by Chinese herbs 11 examples, 7 example survivals are arranged more than 1 year merely; Use prescription therapeutic 11 routine malignant lymphomas such as Herba Hedyotidis Diffusae, Bombyx Batryticatus, Thallus Laminariae (Thallus Eckloniae), 9 examples more than 1 year of wherein surviving, 5 examples more than 3 years, 4 examples more than 5 years, 2 examples more than 10 years.
2. treatment gastritis: Young is with Herba Hedyotidis Diffusae 50g, and Rhizoma Corydalis 10g treats shallow phenotype gastritis 82 examples, result's 5 examples of fully recovering, 14 examples that take a turn for the better, invalid 3 examples.Effective percentage reaches 96.30%.
3. treatment respiratory system infection: with the Herba Hedyotidis Diffusae is main novel formulation " scorching instant granule for curing " (Herba Hedyotidis Diffusae, deer ear grass, duck grass) loaded China pharmacopeia of forming, is mainly used in upper respiratory tract infection, tonsillitis, enteritis etc.
Other: Herba Hedyotidis Diffusae and its medicine compatibility also can be used for treating appendicitis, eczema, psoriasis, pulmonary tuberculosis, liver abscess, venom, urinary system infection etc.
The specific embodiment
Example 1: Herba Hedyotidis Diffusae freeze-dried powder preparation
Prescription Herba Hedyotidis Diffusae 2000.0g, mannitol 100.0g, sodium sulfite 2g, water for injection add to 2000.0ml;
Method for making is learnt from else's experience to check and is met a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd 8 times of amount 1 hour filter, and filtrate merges, reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adds the neutral water stirring and dissolving, leaves standstill 12 hours, and inclining upper strata liquid, centrifugal (4500r/min), be heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 80% ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative (get 100ml put water bath method after residue detect), collect alcohol eluen, decompression recycling ethanol is to 500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds mannitol 100.0g, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add the 2g sodium sulfite again, fully stir evenly, filter, add the injection water to 2000ml, test sample content filters through 0.2 2 μ m microporous filter membrane terminals after pH is qualified again, be sub-packed in the sodium calcium control injection bottle of 10ml, every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.Check is up to specification down by appendix item of 2005 editions pharmacopeia.
A sublimation drying method is adopted in the lyophilization of this technology, the goods solution of anticipating is chilled to-45 ℃ in advance in hothouse, freezing indoor temperature is dropped to-50 ℃ simultaneously, start vacuum pump, after treating that vacuum reaches below the 1.33KPa, slowly open valve, close fridge below the 13.33Pa, slowly heat to-20 ℃ when vacuum in the hothouse reaches.Treat the water evaporates ashes, slowly heat up, change drying again, whole dry run 35 hours at 25 ℃.
Example 2: Herba Hedyotidis Diffusae intravenous fluid
Prescription Herba Hedyotidis Diffusae 2000.0g, chlorobutanol 1g/ polyoxyethylene sorbitan monoleate 20g, sodium sulfite 2g, water for injection add to 2000.0ml;
Method for making is learnt from else's experience to check and is met a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd 8 times of amount 1 hour filter, and filtrate merges, reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adds the neutral water stirring and dissolving, leaves standstill 12 hours, and inclining upper strata liquid, centrifugal (4500r/min), be heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 80% ethanol elution to eluent hydrochloric acid-magnesium powder reaction be negative (get 100ml put water bath method after residue detect) again, collect alcohol eluen, decompression recycling ethanol adds water to 1000ml to 500ml, add proper amount of active carbon, stir evenly, filter, filtrate adds chlorobutanol 1g/ polyoxyethylene sorbitan monoleate 20g, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add the 2g sodium sulfite again, fully stir evenly, filter, add the injection water to 2000ml, test sample content filters through 0.22 μ m microporous filter membrane terminal after pH is qualified again, and embedding is in 2ml or the brown injection bottle of 5ml, sterilization gets final product.Check is up to specification down by appendix item of 2005 editions pharmacopeia.
Example 3: Herba Hedyotidis Diffusae sodium chloride injection
Prescription (1), Herba Hedyotidis Diffusae 100g
(2), sodium chloride 9g
(3), sodium sulfite 250mg
(4), sterile water for injection adds to 1000ml.
Method for making is learnt from else's experience to check and is met a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd 8 times of amount 1 hour filter, and filtrate merges, reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adds the neutral water stirring and dissolving, leaves standstill 12 hours, and inclining upper strata liquid, centrifugal (4500r/min), be heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol is to crude drug volume ratio 2: 1, and thin up (if insoluble matter is arranged, adds 10% sodium hydroxide solution and regulates pH value and make it dissolving to crude drug volume ratio 1: 3-5, but pH value is no more than 7.0), the active carbon that adds 0.1% (g/ml), heated and boiled 15～30 minutes filters, filtrate for later use is measured intermediate content.Take by weighing the sodium chloride of recipe quantity, be dissolved in the water for injection of 90 ℃ of 250-500ml, stirring is dissolved sodium chloride fully, add 0.1% active carbon, insulated and stirred 15 minutes, filtering decarbonization, and regulate in pH value to 5.5～6.5 scopes, measure content, merge with above-mentioned Herba Hedyotidis Diffusae filtrate, regulate pH value to 6.0～7.0, add the active carbon of 0.05% (g/ml) after boiling with 10% sodium chloride solution, kept fluidized state 15～30 minutes, filter, add the injection water, add sodium sulfite to 900ml, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, play filter, the embedding branch is filled in 100ml or the 250ml infusion bottle, and sterilization promptly gets or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, promptly.Check is up to specification down by appendix item of 2005 editions pharmacopeia.
Example 4: Herba Hedyotidis Diffusae glucose injection
Prescription (1), Herba Hedyotidis Diffusae 20-200g
(2), glucose 40-50g
(3), sodium sulfite 500mg
(4), sterile water for injection adds to 1000ml.
Method for making is learnt from else's experience to check and is met a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd 8 times of amount 1 hour filter, and filtrate merges, reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adds the neutral water stirring and dissolving, leaves standstill 12 hours, and inclining upper strata liquid, centrifugal (4500r/min), be heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol was to crude drug volume ratio 2: 1, thin up adds the active carbon of 0.1% (g/ml) to crude drug volume ratio 1: 3-5 (if insoluble matter is arranged, add 10% sodium hydroxide solution adjusting pH value and make it dissolving, but pH value is no more than 7.0), heated and boiled 15～30 minutes, filter, filtrate for later use is measured intermediate content.Take by weighing the glucose of recipe quantity, be added in the water for injection that boils, make into the concentrated solution of 50%-60%, it is an amount of to add hydrochloric acid, adds 0.1% active carbon heated and boiled simultaneously 15～30 minutes, filtering decarbonization, measure content, merge, regulate pH value to 6.0～7.0 with 10% sodium chloride solution with above-mentioned Herba Hedyotidis Diffusae filtrate, the active carbon that adds 0.05% (g/ml) after boiling, kept fluidized state 15～30 minutes, and filtered, add the injection water to 500ml, add sodium sulfite,, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, ultrafiltration divides to be filled in 100ml or the 250ml infusion bottle, sterilization, promptly; Or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, sterilization, promptly.Check is up to specification down by appendix item of 2005 editions pharmacopeia.
Claims (14)
1, intravenous administered formulation of spreading hedyotis herb is characterized in that each raw material and excipient component thereof and makes freeze dried powder in following ratio:
(1), Herba Hedyotidis Diffusae 1500-2500g
(2), excipient is following a kind of composition or multiple mixture of ingredients: mannitol, mannitol lactose, glucose dextran, gelatin hydrolysate are 50-150g
(3), sodium sulfite 1-3g
(4), sterile water for injection adds to 2000ml.
2, intravenous administered formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous fluid in following ratio:
(1), Herba Hedyotidis Diffusae 1500-2500g
(2), chlorobutanol 0.5-1.5g or polyoxyethylene sorbitan monoleate 15-25g, the two selects one,
(3), sodium sulfite 1-3g
(4), sterile water for injection adds to 2000ml.
3, intravenous administered formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous drip liquid in following ratio:
(1), Herba Hedyotidis Diffusae 20-200g
(2), sodium chloride 9g
(3), sodium sulfite 250mg
(4), sterile water for injection adds to 1000ml.
4, intravenous administered formulation of spreading hedyotis herb is characterized in that each raw material components makes intravenous drip liquid in following ratio:
(1), Herba Hedyotidis Diffusae 20-200g
(2), glucose 50g
(3), sodium sulfite 500mg
(4), sterile water for injection adds to 1000ml.
5,, it is characterized in that each raw material components proportioning is according to the described formulation of spreading hedyotis herb of claim 1:
(1), Herba Hedyotidis Diffusae 2000.0g
(2), excipient is following a kind of composition or multiple mixture of ingredients: mannitol, mannitol lactose, glucose dextran, gelatin hydrolysate are 100.0g
(3), sodium sulfite 2g
(4), sterile water for injection adds to 2000.0ml.
6,, it is characterized in that each raw material components proportioning is according to the described formulation of spreading hedyotis herb of claim 2:
(1), Herba Hedyotidis Diffusae 2000.0g
(2), chlorobutanol 1g or polyoxyethylene sorbitan monoleate 20g, select one in two components,
(3), sodium sulfite 2g
(4), sterile water for injection adds to 2000.0ml.
7,, it is characterized in that each raw material components proportioning is according to the described formulation of spreading hedyotis herb of claim 3:
(1), Herba Hedyotidis Diffusae 100.0g
(2), sodium chloride 9g
(3), sodium sulfite 250mg
(4), sterile water for injection adds to 1000ml.
8,, it is characterized in that each raw material components proportioning is according to the described formulation of spreading hedyotis herb of claim 3:
(1), Herba Hedyotidis Diffusae 100.0g
(2), glucose 50g
(3), sodium sulfite 500mg
(4), sterile water for injection adds to 1000ml.
9, the preparation method of formulation of spreading hedyotis herb according to claim 1 or 5 is characterized in that may further comprise the steps:
The check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add alcohol reflux, filtrate decompression backflow ethanol also concentrates, add the neutral water stirring and dissolving, leave standstill, inclining upper strata liquid, centrifugal, be heated to 40-80 ℃, be added on and handle well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, backflow ethanol, add the neutral water heating for dissolving again, dilution is heated to 40-80 ℃, filter while hot, be added on and handle well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, decompression recycling ethanol adds water to 1000ml to 400ml-500ml, adds proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulates pH value 6.5-7.0 with sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content, filter through the microporous filter membrane terminal again, be sub-packed in the sodium calcium control injection bottle of 10ml every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
10, according to the described preparation method of claim 5, it is characterized in that: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add the 65-85% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add the 65-85% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 65-85% ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative (get 100ml put water bath method after residue detect), collect alcohol eluen, decompression recycling ethanol is to 500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content filters through 0.22 μ m microporous filter membrane terminal after pH is qualified again, be sub-packed in the sodium calcium control injection bottle of 10ml, every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
11, according to the described preparation method of claim 5, it is characterized in that: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, backflow ethanol, to relative 1.05-1.10 (60 ℃ of surveys), add neutral water again by crude drug: water is with weight: 1: 1 heating for dissolving of volume ratio, dilution, be heated to 50-60 ℃, filter while hot, by polyamide (40-60 order): crude drug is with volume: weight ratio is added at 1: 2 have been handled well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add 80% ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative (get 100ml put water bath method after residue detect), collect alcohol eluen, decompression recycling ethanol is to 500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds mannitol, regulate pH value 6.5-7.0 with 40% sodium hydroxide solution, add sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content filters through 0.22 μ m microporous filter membrane terminal after pH is qualified again, in the sodium calcium control injection bottle of packing 10ml, every bottle of fill 2ml, lyophilization under the low temperature is rolled lid and is got final product.
12, according to the preparation method of claim 2 or 6 described formulation of spreading hedyotis herb, it is characterized in that may further comprise the steps: the check of learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", is cut into the 2-3cm section, add alcohol reflux, filtrate decompression backflow ethanol also concentrates, and adds the neutral water stirring and dissolving, leaves standstill, incline and upper strata liquid, centrifugal, be heated to 40-80 ℃, be added on and handle well on D101 (AB-8) or the D201 resin column, be washed to water lotion and be closely colourless, discard water lotion; Add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, backflow ethanol, add the neutral water heating for dissolving again, dilution is heated to 40-80 ℃, filter while hot, be added on and handle well on the polyamide column, it is closely colourless to be washed to water lotion, discard water lotion, add ethanol elution to eluent hydrochloric acid-magnesium powder reaction again and be negative, collect alcohol eluen, decompression recycling ethanol is to 400ml-500ml, add water to 1000ml, add proper amount of active carbon, stir evenly, filter, filtrate adds chlorobutanol or polyoxyethylene sorbitan monoleate, regulates pH value 6.5-7.0 with sodium hydroxide solution, adds sodium sulfite again, fully stir evenly, filter, add the injection water to quantitative, test sample content, filter through the microporous filter membrane terminal again, embedding is in 2ml or the brown injection bottle of 5ml, and sterilization gets final product.
13, preparation method according to claim 3 or 7 described formulation of spreading hedyotis herb, the check that it is characterized in that learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol is to crude drug volume ratio 2: 1, and thin up (if insoluble matter is arranged, adds 10% sodium hydroxide solution and regulates pH value and make it dissolving to crude drug volume ratio 1: 3-5, but pH value is no more than 7.0), the active carbon that adds 0.1% (g/ml), heated and boiled 15～30 minutes filters, filtrate for later use is measured intermediate content.Take by weighing the sodium chloride of recipe quantity, be dissolved in the water for injection of 90 ℃ of 250-500ml, stirring is dissolved sodium chloride fully, add 0.1% active carbon, insulated and stirred 15 minutes, filtering decarbonization, and regulate in pH value to 5.5～6.5 scopes, measure content, merge, regulate pH value to 6.0～7.0 with 10% sodium chloride solution with above-mentioned Herba Hedyotidis Diffusae filtrate, the active carbon that adds 0.05% (g/ml) after boiling, kept fluidized state 15～30 minutes, and filtered, add the injection water to 900ml, add sodium sulfite,, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, play filter, the embedding branch is filled in 100ml or the 250ml infusion bottle, sterilization, promptly get or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, promptly.
14. preparation method according to claim 4 or 8 described formulation of spreading hedyotis herb, the check that it is characterized in that learning from else's experience meets a regulation of current edition Chinese Pharmacopoeia " Herba Hedyotidis Diffusae ", be cut into the 2-3cm section, add 80% alcohol reflux 3 times, the 1st time 10 times the amount 2 hours, the 2nd time, the 3rd time 8 times the amount 1 hour, filter, filtrate merges, and reduced-pressure backflow ethanol also is concentrated into relative 1.08-1.12 (60 ℃ of surveys), press crude drug: water is with weight: volume gradation in 1: 2 adding neutral water stirring and dissolving, left standstill 12 hours, inclining upper strata liquid, and centrifugal (4500r/min) is heated to 50-60 ℃, filter while hot, by the portions of resin crude drug with volume: weight ratio is added at 1: 2 have been handled well on D101 (AB-8) or the D201 resin column, is washed to water lotion and is closely colourless, discards water lotion; Add 70% ethanol elution again and react be negative (getting the residue detection after 100ml puts water bath method) to eluent hydrochloric acid-magnesium powder, collect alcohol eluen, decompression recycling ethanol was to crude drug volume ratio 2: 1, thin up adds the active carbon of 0.1% (g/ml) to crude drug volume ratio 1: 3-5 (if insoluble matter is arranged, add 10% sodium hydroxide solution adjusting pH value and make it dissolving, but pH value is no more than 7.0), heated and boiled 15～30 minutes, filter, filtrate for later use is measured intermediate content.Take by weighing the glucose of recipe quantity, be added in the water for injection that boils, make into the concentrated solution of 50%-60%, it is an amount of to add hydrochloric acid, adds 0.1% active carbon heated and boiled simultaneously 15～30 minutes, filtering decarbonization, measure content, merge, regulate pH value to 6.0～7.0 with 10% sodium chloride solution with above-mentioned Herba Hedyotidis Diffusae filtrate, the active carbon that adds 0.05% (g/ml) after boiling, kept fluidized state 15～30 minutes, and filtered, add the injection water to 500ml, add sodium sulfite,, filter, regulate pH value to 6.0～7.0 with 10% sodium hydroxide solution, add to the full amount of water for injection, filter, ultrafiltration divides to be filled in 100ml or the 250ml infusion bottle, sterilization, promptly; Or ultrafiltration, aseptic subpackaged to 100ml or 250ml polypropylene infusion bottle, sterilization, promptly.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102078411A (en) * | 2009-11-30 | 2011-06-01 | 北京振国天仙生物技术有限公司 | Preparation method of spreading hedyotis herb injection |
| CN103610798A (en) * | 2013-11-28 | 2014-03-05 | 中国计量学院 | Active site of oldenlandia diffusa as well as preparation method and application thereof |
-
2005
- 2005-09-13 CN CNB2005100944042A patent/CN100500132C/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102078411A (en) * | 2009-11-30 | 2011-06-01 | 北京振国天仙生物技术有限公司 | Preparation method of spreading hedyotis herb injection |
| CN102078411B (en) * | 2009-11-30 | 2013-09-11 | 北京振国天仙生物技术有限公司 | Preparation method of spreading hedyotis herb injection |
| CN103610798A (en) * | 2013-11-28 | 2014-03-05 | 中国计量学院 | Active site of oldenlandia diffusa as well as preparation method and application thereof |
| CN103610798B (en) * | 2013-11-28 | 2015-11-04 | 中国计量学院 | Active site of a kind of Herba Hedyotidis Diffusae and preparation method thereof, application |
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| Publication number | Publication date |
|---|---|
| CN100500132C (en) | 2009-06-17 |
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