CN1698717A - Chinese medicinal compound fat emulsion injection and its preparation method - Google Patents
Chinese medicinal compound fat emulsion injection and its preparation method Download PDFInfo
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- CN1698717A CN1698717A CN 200510039020 CN200510039020A CN1698717A CN 1698717 A CN1698717 A CN 1698717A CN 200510039020 CN200510039020 CN 200510039020 CN 200510039020 A CN200510039020 A CN 200510039020A CN 1698717 A CN1698717 A CN 1698717A
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Abstract
The invention provides a Chinese medicinal compound fat emulsion injection and its preparation method, wherein the compound recipe comprises flower of honeysuckle, achyranthes and cyathula root, scrophularia root, and Dendrobium nobile. The preparation consists of employing macroscopic adsorption resin technology to isolate and purify the water-soluble and liposoluble positions of the medicinal herbs, and employing emulsification technique to prepare the compound injection.
Description
Technical field
The present invention relates to a kind of Chinese medicine compound fat emulsion injection and preparation method thereof, this Chinese medicine compound comprises Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii four flavor Chinese medicines.The invention belongs to the field of medicine preparations category.
Background technology
Along with China steps into aging society gradually, cardiovascular and cerebrovascular disease is also increasing to China people's influence, at present, China has 1.1 hundred million people to suffer from cardiovascular and cerebrovascular diseases such as hypertension, arteriosclerosis approximately, 6,000 ten thousand people suffer from coronary heart disease, 7,000 ten thousand people suffer from cerebral infarction or cerebral hemorrhage, and the philtrum more than 40 years old has 57% people to suffer from various degree cardiovascular and cerebrovascular disease approximately.Cardiovascular and cerebrovascular disease (as apoplexy, cerebral hemorrhage, heart infarction, coronary heart disease) has the characteristics of high mortality, high relapse rate, high disability rate, brings huge misery for countless families.
MAILUONING ZHUSHEYE is the Chinese medicine compound intravenous injection of thrombosiss such as treatment vasculitis, cerebral thrombosis and sequela thereof, it be with Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii (weight ratio is 1: 1: 1: 1) four flavor Chinese crude drugs are raw material, through water carry, methods such as precipitate with ethanol, ester extraction extract refining forming.Effect with replenishing YIN and removing heat, liver and kidney tonifying, blood circulation promoting and blood stasis dispelling, its mechanism of action is relevant with anticoagulant, thrombolytic, spasmolytic, pain relieving, blood vessel dilating, improvement circulation, adjusting immunity, free radical resisting etc.Through the clinical application practice of more than ten years, be mainly used in treatment coronary heart disease, angina pectoris, arteriosclerosis etc. at present clinically.Because clinical efficacy is definite, obtained in the whole nation using widely.
Because the main active in the MAILUONING ZHUSHEYE of existing existing market is (to see " process of MAILUONING intravenous fluid " through the liposoluble constituent that ethyl acetate extraction obtains, patent publication No.: CN1078148A), be insoluble in water, in order to make the fully dissolving in water of this type of liposoluble constituent, in the preparation process of preparation, added a large amount of Tween 80 hydrotropies, as everyone knows, Tween 80 has very strong hemolytic, cause MAILUONING ZHUSHEYE to have bigger side effect and potential safety hazard in therapeutic process, its case that produces untoward reaction in clinical practice has report also the time.Therefore, adopt the modern Chinese medicine preparation technique, this product is made the Chinese medicine fat emulsion injection that targeting is good, toxic and side effects is little have important practical significance.
In " a kind of process for preparing 'Mailuoning ' injection preparation " (patent publication No.: disclose many weak points CN1555854), and disclose improving one's methods of oneself to the preparation technology of existing MAILUONING ZHUSHEYE.Though the more existing MAILUONING ZHUSHEYE of its preparation method has bigger improvement, also has tangible weak point: it requires Radix Achyranthis Bidentatae and Radix Scrophulariae " pure water is two to be carried ", and macroporous resin column gets extract A on the alcohol extract, and the water extract gets extract B through precipitate with ethanol; Flos Lonicerae water warm macerating, Herba Dendrobii elder generation water is proposed alcohol extraction again, and the water extract is precipitate with ethanol again.Although whole technology is more abundant to the extraction of effective ingredient, but it is very loaded down with trivial details, especially it is obviously irrational the alcohol extract of Radix Achyranthis Bidentatae and Radix Scrophulariae being handled through purification with macroreticular resin, as everyone knows, the General Principle of purification with macroreticular resin Chinese medicine extract is with after the effective ingredient absorption in aqueous solution, earlier by the washing remove impurity, reach the purpose of purification again by ethanolysis absorption, and this method directly goes up macroporous resin column with alcohol extract, because effective ingredient can't adsorb on macroporous resin in pure liquid, so this method is difficult to reach the effect of purification.
Summary of the invention
Many-sided weak point at existing MAILUONING ZHUSHEYE existence, the invention provides a kind of easy and can reach the preparation method of fine purification effect, and finally adopt the modern Chinese medicine preparation technique, the extract that purification obtains is made the Chinese medicine fat emulsion injection.
The object of the present invention is to provide a kind of Chinese medicine compound fat emulsion injection preparation and preparation method thereof, further improve the safety and the curative effect of preparation.
Another object of the present invention is to provide a kind of Chinese medicine compound preparation method of extract.
Chinese medicine compound fat emulsion injection among the present invention, it is characterized in that: this injection is made by extract and adjuvant oil for injection, emulsifying agent, isoosmotic adjusting agent and the water for injection of Chinese medicine Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, the weight ratio of four flavor principal agent Flos Loniceraes wherein, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii is 1: 1: 1: 1, and its prescription is as follows:
Flos Lonicerae 0.1～15kg
Radix Achyranthis Bidentatae 0.1～15kg
Radix Scrophulariae 0.1～15kg
Herba Dendrobii 0.1～15kg
Oil for injection 10～500g
Emulsifying agent 5～50g
Isoosmotic adjusting agent 0.5～50g
Water for injection adds to 1000ml
The prescription of preferred Chinese medicine compound fat emulsion injection is:
Flos Lonicerae 1～5kg
Radix Achyranthis Bidentatae 1～5kg
Radix Scrophulariae 1～5kg
Herba Dendrobii 1～5kg
Oil for injection 50～200g
Emulsifying agent 10～25g
Isoosmotic adjusting agent 1～25g
Water for injection adds to 1000ml
Preferred Chinese medicine compound fat emulsion injection prescription is:
Flos Lonicerae 2.5kg
Radix Achyranthis Bidentatae 2.5kg
Radix Scrophulariae 2.5kg
Herba Dendrobii 2.5kg
Oil for injection 100g
Emulsifying agent 12g
Isoosmotic adjusting agent 22.5g
Water for injection adds to 1000ml
Used oil for injection is soybean oil, Oleum Gossypii semen, safflower oil, fish oil, Oleum sesami, olive oil, C in the above-mentioned prescription
8～C
14MCT Oil or one or more the mixture in the short-chain fatty acid triglyceride with any mixed, preferred soybean oil;
Described emulsifying agent is selected from phospholipid or non-ionic surface active agent Planck Buddhist nun 188F
68In one or more mixture with any mixed, the phospholipid preferably lecithin comprises Ovum Gallus domesticus Flavus lecithin, soybean lecithin and hydrolecithin, more preferably Ovum Gallus domesticus Flavus lecithin;
Described isoosmotic adjusting agent is selected from one or more mixture with any mixed in glycerol, mannitol, xylitol, sorbitol or the glucose, preferably glycerine.
Chinese medicine compound preparation method of extract of the present invention is as follows:
Extracting honeysuckle, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, pulverize (weight ratio is 1: 1: 1: 1), be prepared by the following method:
1, above medical material pulverize separately is become coarse powder, add 5～10 times of amounts of 10～80% alcoholic solution behind the mixing and extract 2～4 times, each 1～3 hour, merge extractive liquid.
2, the extracting solution concentrating under reduced pressure is removed ethanol after, thin up to 10～30 times medical material volume (M/V) leaves standstill, and puts coldly, filters.
3, get filtrate, last macroporous adsorptive resins after upper prop finishes, adds water and fully is eluted to the solution clarification.Collect the aqueous solution that upper prop and eluting produce.
4, with 50%～95% ethanol elution macroporous adsorptive resins, collect eluent, and be evaporated to dried, extract A (being mainly little polarity fat-soluble active ingredient).
5, get the aqueous solution that middle upper prop of step " 3 " and eluting produce, be evaporated to 0.1～2 times of medical material volume (M/V), put cold, the alcoholic solution that under the state that stirs, slowly adds 0.5～5 times of medical material volume (M/V), leave standstill, filter, collect filtrate, and drying under reduced pressure gets extract B (being mainly the water-soluble active ingredient of high polarity) to doing.
Above-mentioned described preparation method is characterized in that, the big pore adsorption resin model is polarity, Semi-polarity and low pole or nonpolar macroporous adsorption resin.
The preparation method of Chinese medicine compound fat emulsion injection preparation of the present invention can have following two kinds of methods:
Method one
Under nitrogen protection, take by weighing oil for injection, be heated to 40～80 ℃, under high-speed stirred, emulsifying agent, extract A are added in the oil for injection, stir as oil phase; In addition isoosmotic adjusting agent is added in the proper amount of water for injection, mixing adds extract B, fully after the stirring and dissolving with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 5.0～8.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Method two
Under nitrogen protection, take by weighing oil for injection, be heated to 40～80 ℃, under high-speed stirred, emulsifying agent, extract A are added in the oil for injection, stir as oil phase; In addition isoosmotic adjusting agent is added in the proper amount of water for injection, behind the mixing with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 5.0～8.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Below by to MAILUONING fat emulsion injection and former MAILUONING ZHUSHEYE to the comparison of coronary artery ligation rat model protective effect, further specify advantage of the present invention.
1. experimental technique:
Get rat, body weight 200～300g is divided into normal group, model group, MAILUONING ZHUSHEYE group, MAILUONING Emulsion injection group at random.After the animal lumbar injection pentobarbital sodium 40mg/kg anesthesia, the circulation of qi promoting cannula, connect artificial respirator, practice artificial respiration,, expose the thoracic cavity with expander at left breast fourth, fifth intercostal incision skin and Musclar layer, cut off pericardium, offset distance opening part 2～3mm place closes the thoracic cavity with medical no wound stitching thread ligation coronary artery before coronary artery, and the electrocardiogram two ST section of leading is not obviously raised the person and taken.
The normal group animal is except that not ligation coronary artery, and other operation processs are identical with model group, promptly causes sham-operation.Suture muscles layer and skin layer after ligation coronary artery or sham-operation finish, tail vein injection saline or medicinal liquid (normal group: normal saline 1ml/kg; Model group: normal saline 1ml/kg; MAILUONING group: MAILUONING 10g/kg; MAILUONING Emulsion group: MAILUONING 10g/kg, intraperitoneal injection of saline or medicinal liquid (dosage is the same) once more after 4 hours.The pneumoretroperitoneum vein was got blood in 24 hours, got blood serum sample through centrifugalize, measured lactic acid dehydrogenase (LDH) and creatine phosphokinase (CK) vigor, and respectively organized difference.After getting blood, take out rat heart immediately, clean hematocele in the chambers of the heart with normal saline, remove atrium and fat, claim the left heart and heavy whole-heartedly, with 5～8 of myocardium of left ventricle crosscuts, put into test tube, the about 3ml of phosphate buffer that adds chloride NBT (5mg/ml) again in the test tube, put in 37 ℃ of waters bath with thermostatic control and dyeed about 10 minutes, treat to clean with normal saline behind the tissue staining, cut ischemic tissue's (not dyeing or lark) and weigh, the calculation infarcted myocardium accounts for percentage by weight whole-heartedly, and respectively organizes difference.
2. experimental result
As seen from Table 1, MAILUONING ZHUSHEYE and MAILUONING Emulsion injection all can dwindle myocardial infarction area, and as seen from Table 2, MAILUONING ZHUSHEYE and MAILUONING Emulsion injection all can significantly reduce Serum LDH and CK level.Above results suggest, MAILUONING ZHUSHEYE and MAILUONING Emulsion injection all have certain therapeutical effect to the ischemic myocardial infraction that rat ligation coronary artery causes, and (10g/kg) MAILUONING Emulsion injection drug effect is better than MAILUONING ZHUSHEYE under Isodose.
Tab 1. MAILUONING ZHUSHEYE and MAILUONING Emulsion injection are to the influence of coronary artery ligation rat model myocardial infarction area (x ± S)
| Group | ??N | Dosage (g/kg) | Infarcted myocardium percentage ratio (%) |
| The normal control group | ??10 | ??- | ??0±0 |
| Model control group | ??10 | ??- | ??30.1±8.4 |
| The MAILUONING ZHUSHEYE group | ??10 | ??10 | ??16.6±4.6 ** |
| MAILUONING Emulsion injection group | ??10 | ??10 | ??13.0±2.5 **# |
*Compare with model control group P＜0.01, and compare with the MAILUONING ZHUSHEYE group #P＜0.5
Tab 2. MAILUONING ZHUSHEYE and MAILUONING Emulsion injection are to the influence of coronary artery ligation rat model Serum LDH and CK level (x ± S)
| Group | ??N | Dosage (g/kg) | ??LDH ??(U/L) | ??CK ??(U/ml) |
| The normal control group | ??10 | ??- | ??5933.3±866.7 | ??67.8±25.0 |
| Model control group | ??10 | ??- | ??8625.9±1135.7 | ??383.1±42.9 |
| The MAILUONING ZHUSHEYE group | ??10 | ??10 | ??7069.1±910.0 ** | ??133.5±29.4 ** |
| MAILUONING emulsion injection group | ??10 | ??10 | ??6036.1±1192.1 **# | ??105.4±25.9 **# |
*Compare with model control group P＜0.01, and compare with the MAILUONING ZHUSHEYE group #P＜0.5
The Chinese medicine compound fat emulsion injection of the present invention's preparation is compared with former Chinese medicine compound injection, and following significant advantage is arranged:
1, extraction is more abundant: the characteristics that liposoluble constituent is arranged again according to the existing water soluble ingredient of active component of four Chinese medicine material in this prescription, the present invention has selected certain density ethanol for use when extracting be extraction solvent, guarantees that fat-soluble active ingredient and water-soluble active ingredient all can be extracted fully.
2, purification is more reasonable: the present invention adopt earlier the macroporous adsorbent resin technology respectively to fat-solublely carry out enrichment, separate with water soluble ingredient, purification, purification effect is good, the resource utilization height has been avoided the waste of herb resource.
3. curative effect is more definite: the present invention has adopted emulsifying technology, and breast grain particle diameter must not have the particle greater than 5 μ m, more helps the absorption of medicine and sees through blood brain barrier, acts on rapider, stable.
4. safety is good: this product does not re-use the very strong Tween 80 of hemolytic owing to adopted emulsifying technology in the prescription, improved the safety of medication.
The present invention is directed to many shortcomings of former Chinese medicine compound injection, purification by macroporous resin technology, high-pressure emulsification technology etc. in preparation technology, have been adopted, in preparation process, do not re-use Tween 80, prepared Chinese medicine compound fat emulsion injection curative effect is more definite, effect is rapider, it is safer to use, the fat emulsion injection prepared according to method of the present invention can directly see through blood brain barrier, and arteriosclerosis, cerebral thrombosis and sequela thereof etc. are had better curative effect.
The specific embodiment of form is described in further detail foregoing of the present invention more by the following examples, but should not be interpreted as at this point that the scope of the above-mentioned theme of the present invention only limits to following examples.Do not breaking away under the above-mentioned technology prerequisite of the present invention, replacing or the modification of change according to corresponding being equal to that ordinary skill knowledge and customary means are made, including in the scope of content of the present invention.
The specific embodiment
Embodiment 1
Difference extracting honeysuckle 2.5kg, Radix Achyranthis Bidentatae 2.5kg, Radix Scrophulariae 2.5kg, Herba Dendrobii 2.5kg, pulverize, mixing adds 5 times of amounts of ethanol reflux, extract, of 10% 2 times, each 2 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 200L again, put cold, filter, filtrate is crossed the HPD-100 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 50% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 2.5L, put coldly, under the state that stirs, slowly add the 10L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, take by weighing injection soybean oil 100g, be heated to 60 ℃, under high-speed stirred, Ovum Gallus domesticus Flavus lecithin 12g, extract A are added in the oil for injection, stir as oil phase; In addition glycerol 22.5g is added in the proper amount of water for injection, mixing adds extract B, fully after the stirring and dissolving with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 7.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Embodiment 2
Difference extracting honeysuckle 0.1kg, Radix Achyranthis Bidentatae 0.1kg, Radix Scrophulariae 0.1kg, Herba Dendrobii 0.1kg, pulverize, mixing adds 7 times of amounts of ethanol reflux, extract, of 30% 4 times, each 1.0 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 8.0L again, put cold, filter, filtrate is crossed the AB-8 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 85% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 0.5L, put coldly, under the state that stirs, slowly add the 2L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, take by weighing injection C
14MCT Oil 10g is heated to 40 ℃, under high-speed stirred soybean phospholipid 15g, extract A is added in the oil for injection, stirs as oil phase; In addition glycerol 2g and glucose 3g are added in the proper amount of water for injection, mixing adds extract B, fully after the stirring and dissolving with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 5.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Embodiment 3
Difference extracting honeysuckle 0.2kg, Radix Achyranthis Bidentatae 0.2kg, Radix Scrophulariae 0.2kg, Herba Dendrobii 0.2kg, pulverize, mixing adds 10 times of amounts of ethanol reflux, extract, of 25% 2 times, each 2 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 10L again, put cold, filter, filtrate is crossed the D-1300 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 95% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 0.8L, put coldly, under the state that stirs, slowly add the 2.0L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, take by weighing injection safflower oil 10g, be heated to 80 ℃, under high-speed stirred, Ovum Gallus domesticus Flavus lecithin 15g, extract A are added in the oil for injection, stir as oil phase; In addition glycerol 0.5g is added in the proper amount of water for injection, mixing, with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 6.8, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Embodiment 4
Difference extracting honeysuckle 1.0kg, Radix Achyranthis Bidentatae 1.0kg, Radix Scrophulariae 1.0kg, Herba Dendrobii 1.0kg, pulverize, mixing adds 5 times of amounts of ethanol reflux, extract, of 80% 3 times, each 3 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 60L again, put cold, filter, filtrate is crossed the D-3520 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 50% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 1.0L, put coldly, under the state that stirs, slowly add the 5L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, add the injection soybean oil of 50g, the mixed solution of Oleum Gossypii semen, be heated to 50 ℃, under high-speed stirred with Planck Buddhist nun 188F
685.0g, extract A adds in the oil for injection, stir as oil phase; In addition glycerol 1.0g is added in the proper amount of water for injection, mixing, with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 7.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Embodiment 5
Difference extracting honeysuckle 5kg, Radix Achyranthis Bidentatae 5kg, Radix Scrophulariae 5kg, Herba Dendrobii 5kg, pulverize, mixing adds 7 times of amounts of ethanol reflux, extract, of 40% 3 times, each 1.5 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 300L again, put cold, filter, filtrate is crossed the AB-8 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 95% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 10L, put coldly, under the state that stirs, slowly add the 40L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, take by weighing injection fish oil 200g, be heated to 60 ℃, under high-speed stirred, Ovum Gallus domesticus Flavus lecithin 15g, soybean phospholipid 10g, extract A are added in the oil for injection, stir as oil phase; In addition mannitol 10g is added in the proper amount of water for injection, mixing adds extract B, fully after the stirring and dissolving with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 7.5, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Embodiment 6
Difference extracting honeysuckle 15kg, Radix Achyranthis Bidentatae 15kg, Radix Scrophulariae 15kg, Herba Dendrobii 15kg, pulverize, mixing adds 5 times of amounts of ethanol reflux, extract, of 50% 3 times, each 2 hours, after the extracting solution concentrating under reduced pressure is removed ethanol, add water to 800L again, put cold, filter, filtrate is crossed the HPD-400 macroporous adsorptive resins, adds water elution to eluent and clarifies, and collects the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 75% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 15L, put coldly, under the state that stirs, slowly add the 60L alcoholic solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
Under nitrogen protection, add the injection Oleum Gossypii semen of 500g, be heated to 70 ℃, under high-speed stirred, Ovum Gallus domesticus Flavus lecithin 50g, extract A are added in the oil for injection, stir as oil phase; In addition glucose 50g is added in the proper amount of water for injection, mixing, with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is after the high pressure homogenize breast is even, regulate pH to 7.0, mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, and promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m no more than 3%.After the filtration, fill, logical nitrogen, seal, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
Claims (16)
1, a kind of Chinese medicine compound fat emulsion injection is characterized in that: this injection is made by Chinese medicine compound extract and adjuvant oil for injection, emulsifying agent, isoosmotic adjusting agent and the water for injection of four flavor Chinese medicine Flos Loniceraes, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii preparation.
2, Chinese medicine compound fat emulsion injection according to claim 1 is characterized in that: every 1000ml fat emulsion injection by etc. Chinese medicine Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii and adjuvant oil for injection, emulsifying agent, the isoosmotic adjusting agent of weight ratio make by following inventory:
Flos Lonicerae 0.1～15kg
Radix Achyranthis Bidentatae 0.1～15kg
Radix Scrophulariae 0.1～15kg
Herba Dendrobii 0.1～15kg
Oil for injection 10～500g
Emulsifying agent 5～50g
Isoosmotic adjusting agent 0.5～50g
3, Chinese medicine compound fat emulsion injection according to claim 1 is characterized in that: every 1000ml fat emulsion injection by etc. Chinese medicine Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii and adjuvant oil for injection, emulsifying agent, the isoosmotic adjusting agent of weight ratio make by following inventory:
Flos Lonicerae 1～5kg
Radix Achyranthis Bidentatae 1～5kg
Radix Scrophulariae 1～5kg
Herba Dendrobii 1～5kg
Oil for injection 50～200g
Emulsifying agent 10～25g
Isoosmotic adjusting agent 1～25g
4, Chinese medicine compound fat emulsion injection according to claim 1 is characterized in that: every 1000ml fat emulsion injection by etc. Chinese medicine Flos Lonicerae, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii and adjuvant oil for injection, emulsifying agent, the isoosmotic adjusting agent of weight ratio make by following inventory:
Flos Lonicerae 2.5kg
Radix Achyranthis Bidentatae 2.5kg
Radix Scrophulariae 2.5kg
Herba Dendrobii 2.5kg
Oil for injection 100g
Emulsifying agent 12g
Isoosmotic adjusting agent 22.5g
5, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: oil for injection is soybean oil, Oleum Gossypii semen, safflower oil, fish oil, Oleum sesami, olive oil, C
8～C
14MCT Oil or one or more the mixture in the short-chain fatty acid triglyceride with any mixed.
6, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: oil for injection is a soybean oil.
7, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: emulsifying agent is selected from phospholipid or non-ionic surface active agent Planck Buddhist nun 188F
68In one or more mixture with any mixed.
8, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: emulsifying agent is a lecithin, comprises Ovum Gallus domesticus Flavus lecithin, soybean lecithin and hydrolecithin.
9, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: emulsifying agent is an Ovum Gallus domesticus Flavus lecithin.
10, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: isoosmotic adjusting agent is selected from one or more mixture with any mixed in glycerol, mannitol, xylitol, sorbitol or the glucose.
11, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: isoosmotic adjusting agent is a glycerol.
12, Chinese medicine compound fat emulsion injection according to claim 1 is characterized in that: described Chinese medicine compound preparation method of extract is:
By prescription extracting honeysuckle, Radix Achyranthis Bidentatae, Radix Scrophulariae, Herba Dendrobii, pulverize mixing, add 5～10 times of amount 10～80% alcohol reflux 2～4 times, each 1～3 hour, after the extracting solution concentrating under reduced pressure is removed ethanol, add the water dilution of 10～30 times of medical material volumes again, leave standstill, put coldly, filter, filtrate is crossed macroporous adsorptive resins, add water elution to eluent and clarify, collect the water liquid that produces in upper prop and the elution process; The macroporous adsorptive resins that water elution finishes adds 50%～95% ethanol elution, collects eluent, reclaims ethanol to doing, and gets extract A; Get the water liquid that produces in upper prop and the elution process, be evaporated to 0.1～2 times of medical material volume, put coldly, under the state that stirs, slowly add 0.5～5 times of medical material volume ethanol solution, leave standstill, filter, collect filtrate and drying under reduced pressure to doing, extract B.
13, preparation method according to claim 12 is characterized in that: the big pore adsorption resin model is polarity, Semi-polarity and low pole or nonpolar macroporous adsorption resin.
14, macroporous resin according to claim 13 is characterized in that: the macroporous resin model is HPD-100, D-3520, D-1300, AB-8, HPD-400.
15, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that: the preparation method of said preparation is:
Under nitrogen protection, take by weighing oil for injection, be heated to 40～80 ℃, under high-speed stirred, emulsifying agent, extract A are added in the oil for injection, stir as oil phase; In addition isoosmotic adjusting agent is added in the proper amount of water for injection, mixing adds extract B, fully after the stirring and dissolving with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is regulated pH to 5.0～8.0 after the high pressure homogenize breast is even, and mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m is no more than 3%, after the filtration, fill, logical nitrogen, seals, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
16, according to the described Chinese medicine compound fat emulsion injection of arbitrary claim in the claim 1 to 4, it is characterized in that the preparation method of said preparation also can be:
Under nitrogen protection, take by weighing oil for injection, be heated to 40～80 ℃, under high-speed stirred, emulsifying agent, extract A are added in the oil for injection, stir as oil phase; In addition isoosmotic adjusting agent is added in the proper amount of water for injection, behind the mixing with the membrane filtration of 0.45 μ m as water; Under high-speed stirred, oil phase is mixed with water and continue high-speed stirred and make colostrum, add the injection water to 1000ml, mixing is regulated pH to 5.0～8.0 after the high pressure homogenize breast is even, and mixing is after the high pressure homogenizer homogenize is qualified to the breast grain, promptly breast grain particle diameter must not have the particle greater than 5 μ m, the above particle of 1 μ m is no more than 3%, after the filtration, fill, logical nitrogen, seals, put in the rotary steam steriliser and sterilize, after the cooling, packing promptly gets the Chinese medicine compound fat emulsion injection.
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| CN 200510039020 CN1698717B (en) | 2005-04-22 | 2005-04-22 | Chinese medicinal compound fat emulsion injection and its preparation method |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101085227B (en) * | 2006-06-08 | 2011-10-26 | 天津天士力之骄药业有限公司 | Composition for treating angitis, preparation and its preparation method |
| CN101085225B (en) * | 2006-06-08 | 2011-11-30 | 天津天士力之骄药业有限公司 | Composition for treating angitis, preparation and its preparation method |
| CN101194999B (en) * | 2006-12-08 | 2012-03-28 | 天津天士力制药股份有限公司 | Nano-emulsion for treating angitis and method for preparing the same |
| CN105770090A (en) * | 2014-12-22 | 2016-07-20 | 贵州益佰女子大药厂有限责任公司 | Milin fat emulsion injection and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1033211C (en) * | 1992-12-15 | 1996-11-06 | 南京金陵制药厂 | Process for preparing intravenous injection' Mailuoning |
| CN1554397A (en) * | 2003-12-26 | 2004-12-15 | 济南永曜医药科技有限公司 | Pulse and channel drop pill and soft capsule and its preparing method |
-
2005
- 2005-04-22 CN CN 200510039020 patent/CN1698717B/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101085227B (en) * | 2006-06-08 | 2011-10-26 | 天津天士力之骄药业有限公司 | Composition for treating angitis, preparation and its preparation method |
| CN101085225B (en) * | 2006-06-08 | 2011-11-30 | 天津天士力之骄药业有限公司 | Composition for treating angitis, preparation and its preparation method |
| CN101194999B (en) * | 2006-12-08 | 2012-03-28 | 天津天士力制药股份有限公司 | Nano-emulsion for treating angitis and method for preparing the same |
| CN105770090A (en) * | 2014-12-22 | 2016-07-20 | 贵州益佰女子大药厂有限责任公司 | Milin fat emulsion injection and preparation method thereof |
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