CN1241555C - Elemene fatty emulsion injection and preparing method thereof - Google Patents
Elemene fatty emulsion injection and preparing method thereof Download PDFInfo
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- CN1241555C CN1241555C CN 02155072 CN02155072A CN1241555C CN 1241555 C CN1241555 C CN 1241555C CN 02155072 CN02155072 CN 02155072 CN 02155072 A CN02155072 A CN 02155072A CN 1241555 C CN1241555 C CN 1241555C
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Abstract
The present invention belongs to the technical field of medicinal preparations, which discloses an elemene fatty emulsion injection. The preparation comprises 0.05 to 0.25% of elemene, 10 to 30% of injection soybean oil, 1.0 to 1.5% of injection yolk-lecithin or 0.8 to 1.5% of injection granulesten, 2.0 to 2.5% of injection glycerine and 100 ml of injection water. The preparation of the present invention has killing effects on various tumour cells and provides high-energy nutrients for human bodies. When the present invention is used, the degree of irritative pain of veins is low. The present invention provides a preparation method.
Description
Technical field:
The invention belongs to technical field of medicine.Be specifically related to a kind of elemene fat emulsion injection and preparation method.
Background technology:
Elemene is the anticancer active ingredient of extracting from zingiberaceous plant Radix Curcumae (Rhizoma Curcumae), is Main Ingredients and Appearance with the beta-elemene, contains a small amount of δ, γ-elemene and terpenoid thereof simultaneously.
Motherland's medicine thinks that Rhizoma Curcumae is warm in nature, bitter in the mouth is hot, and circulation of qi promoting removing blood stasis, removing food stagnancy pain relieving, antitumor efficacy are arranged.Sixties end, carry out anticancer test and also see report.Early seventies has the people that Rhizoma Curcumae volatile oil topical application treatment cervical cancer is had certain curative effect.Dalian Medical House produces Rhizoma Curcumae at early seventies with Wenzhou and carries out anticancer experimentation, finds that its volatile oil has obvious therapeutic effect to various mouse interior tumors, elemene has been made injection and oral liquid.But this injection system is solubilizing agent with tween 80, and content does not meet the relevant tween 80 consumption regulation of country up to 10%.Improving so Dalian Medical House carries out dosage form again, is that emulsifying agent is made elemene emulsion injection (20ml: 100mg), can be used for thoracic cavity and intravenously administrable with phospholipid.
1996, elemene emulsion injection obtained national Western medicine two kind new medicine certificates, and its authentication code is (ws-049 (x-041)-96-(2)).Through the clinical practice of examples up to ten thousand, confirm that this product has antitumous effect, to the treatment cancerous ascites pleural fluid, intracranial tumor, hepatocarcinoma have good result, and can alleviate cancerous pain and the effect of human body immunity improving power, are a kind of non-cytotoxicity broad-spectrum anti-tumor new drug.But when intravenously administrable, have serious venous stimulation and pain, the phlebitis incidence rate can't stand the patient up to about 30%.Use for reference abroad vein irritating big medicine such as anesthetics propofol, rely on rice ester etc. to be dissolved in to make oil in water emulsion in the oil phase to reduce the phlebitic incidence rate and the degree that eases the pain.
Summary of the invention:
Technical problem to be solved by this invention is to overcome above-mentioned weak point, and the novel formulation of design elemene improves drug effect, reduces side effect.
The invention provides a kind of elemene fat emulsion injection, the weight % of this injection forms and comprises that elemene 0.05～0.25%, injection soybean oil 10～30%, injection Ovum Gallus domesticus Flavus lecithin 1.0～1.5 or injection soybean phospholipid 0.8～1.5%, glycerol for injection 2.0～2.5%, water for injection add to 100ml.
Injection of the present invention is an oil in water emulsion, and 250ml: 250mg, its consumption are elemene 250～750mg at every turn.Confirm that through pharmacological testing its vein irritating and pain degree alleviate than existing preparation.And soybean oil is made solvent, lecithin is made emulsifying agent, makes it can also provide nutritions such as human body heat energy and essential fatty acid when clinical treatment because of this preparation adopts, and still has clinical nutrition and supports effect.
Elemene injection of the present invention is as follows to animal pain and vascular stimulation result of the test:
1, tried thing:
Compound method: 10% fat emulsion injection contains 0.1% elemene (I number), 20% fat emulsion injection contains 0.1% elemene (II number) and 20% fat emulsion injection contains 6% dextrorotation candy acid anhydride and three samples of 0.1% elemene (III number) all adopt stock solution.Dilute with normal saline with reference to the former elemene emulsion injection of product, elemene concentration is diluted to 0.1% (IV) from 0.5%.
2, content of the test:
(1) mouse writhing test:
Laboratory animal: kunming mice, test 10～20, male and female half and half for every group.
Dosage and route of administration: I, II and III number three elemene fat emulsion injection liquid samples all adopt a stock solution 1ml/ mice, i.e. 1mg/ mice.Adopt normal saline dilution back elemene concentration 1m/1mIV sample with reference to the former elemene emulsion injections of product (now being renamed as elemene injection), administration concentration also is a 1ml/ mice, i.e. 1mg/ mice.Each sample test solution all adopts the abdominal channels administration.(remarks: the volume of abdominal channels administration is a 0.5ml/ mice routinely, and the trial test of this experiment is found to be tried thing if " turning round body " reaction do not occur for 0.5ml/0.5mg/ mice.For reinforcement is tried the stressed condition of thing, the volume of its administration is increased to 1ml/ mice).
The mouse writhing test method: under 20 ℃ ± 2 ℃ conditions of room temperature, injected in the mouse peritoneal by test solution, make mice because of stimulation cause the abdominal part deep, the persistent pain reaction of large tracts of land.The number of times that produces " turning round body " (abdominal part indent, trunk are upheld with back leg, hips up) in the mice 0～15 minute and 15～30 minutes is respectively organized in statistical observation, organizes mice and causes the number of times of " turning round body " with each, adds up.
The mouse writhing result of the test: three screened I, II, III number three elemene fat emulsion injection liquid samples stimulate mouse writhing and do not occur reaction substantially, and they stimulate the fairly obvious former elemene emulsion injection IV that is lower than to mouse writhing.See table 1 for details.
Table 1 mouse writhing test (1) n=5; (2) n=10
| Sample | Female Mus is turned round body and counts X ± SD | Male Mus is turned round body and counts X ± SD | ||
| 0～15 minute | 15～30 minutes | 0～15 minute | 15～30 minutes | |
| Former Elemenum Emulsion IV number | (1)13.6±11.1 (2)12.4±7.5 | (1)0.4±0.8 (2)0.2±0.4 | (1)3.2±6.4 (2)5.3±5.2 | (1)1.4±0.9 (2)0.8±1.0 |
| 10% Elemenum Emulsion I number | (1)2.2±4.9 (2)0.6±1.2 | (1)0 (2)0 | (1)0 (2)0 | (1)0 (2)0 |
| 20% Elemenum Emulsion II number | (1)0 (2)0 | (1)0 (2)0 | (1)0 (2)0 | (3)0 (4)0 |
| 20% breast+low right III number | (1)0 (2)0 | (1)0 (2)0 | (1)0 (2)0 | (1)0 (2)0 |
Annotate: 1, experimental result represented respectively twice in parantheses interior 1 and 2
2, test 10 of every group of mices the 1st time, the 2nd time 20 every group, equal male and female half and half.
(2) the mice hot plate causes the pain test:
Laboratory animal: kunming mice, body weight 20 ± 2 grams are tested 10～20, male and female half and half for every group.
Dosage and route of administration: I, II and III number three elemene fat emulsion injection liquid samples all adopt a stock solution 0.3ml/ mice, i.e. 0.3mg/ mice.Reference substance IV administration concentration also is a 0.3ml/ mice, i.e. 0.3mg/ mice.Each sampling test all adopts right back toes subcutaneous administration.
The mice hot plate causes the pain test method: behind the mice behind the toes subcutaneous injection 0.03ml test solution, place on 20 ℃ ± 1 ℃ the hot plate, observe the number of times that pain appears occurring in 5 minutes after time of pain reaction and the administration in mice, gained result and former elemene emulsion injection relatively calculate by following formula.
The standard of drafting: licked No. 1 meter of foot 2 minutes
Carry No. 1 meter of foot 1 minute
Above-mentioned action surpasses 5 minutes continuously and adds up 1 time
Stimulation time appears: promptly begin foot to occur licking or carry the sufficient time (second)
The percentage rate that inhibition stimulates=
[(positive group stimulates score-test group to stimulate score)/positive group stimulates meter] divides * 100%
The rate elongation of appearance stimulation time=
[stimulation time appears in (test group stimulation time-positive group occurs and stimulation time occurs)/positive group] * 100%
The mice hot plate method causes pain result of the test: I, II, III number three screened elemene injection sample and the mice hot plate is caused time or the pain that to stimulate appear in pain reaction for the first time all is starkly lower than former elemene emulsion injection reference substance IV number, and the result sees table 2,3,4 for details.
The mice hot plate test:
Table 2:n=10 (male and female half and half)
| Sample | Stimulation time (second) appears | Stimulate integration | ||||
| Female | Male | Grand average | Female | Male | Total points | |
| Former Elemenum Emulsion | 27.2±2.0 | 34±13.9 | 30.6 | 22.9±16.2 | 14.8±7.1 | 18.85 |
| 10% Elemenum Emulsion | 71.2±19.5 | 65.8±22.6 | 68.5 | 5.3±4.1 | 2.4±1.9 | 3.85 |
| 20% Elemenum Emulsion | 84.6±26.9 | 83.0±31.2 | 83.8 | 4.4±4.2 | 1.0±1.3 | 2.70 |
| 20% breast+low right | 96.4±48.0 | 119.2±1.6 | 107.8 | 2.6±3.8 | 0.2±0.6 | 1.40 |
Table 2:n=10 (male and female half and half)
| Sample | Stimulation time (second) appears | Stimulate integration | ||||
| Female | Male | Grand average | Female | Male | Total points | |
| Former Elemenum Emulsion | 39.6±11.2 | 21.6±2.0 | 30.6 | 27.1±12.0 | 21.9816.6 | 24.5 |
| 10% Elemenum Emulsion | 58.0±9.5 | 64.2±35.7 | 61.1 | 6.7±2.3 | 5.1±3.4 | 5.9 |
| 20% Elemenum Emulsion | 82.4±20.9 | 83.8±33.7 | 83.1 | 2.8±2.8 | 1.4±2.4 | 2.1 |
| 20% breast+low right | 95.2±18.4 | 104.6±31 | 99.9 | 6.0±11.8 | 0.1±0.3 | 3.05 |
Table 3
| Sample | Stimulation time rate elongation % appears | Stimulate suppression ratio % | ||
| The 1st time | The 2nd time | The 1st time | The 2nd time | |
| 10% Elemenum Emulsion | 123.8 | 99.6 | 79.5 | 75.9 |
| 20% Elemenum Emulsion | 173.8 | 171.5 | 85.6 | 91.4 |
| 20% breast+low right | 252.2 | 226.4 | 92.5 | 87.5 |
Annotate 1: above data all compare with former elemene emulsion injection.
(3) irritant test of rabbit auricular vein continuous drip:
Laboratory animal: rabbit No. 6, body weight 2.5～3.0kg, male.
Dosage and route of administration: I sample every day instils with 20～25ml/1h auricular vein, every day dosage 10mg/kg, successive administration 8 days, accumulated dose is 80mg/kg.Reference substance IV sample is with identical dosage administration.Negative control group is a normal saline.
Rabbit auricular vein irritant test result:
Gross examination of skeletal muscle: do not see obvious auricular vein irritant reaction in preceding 3 days of administration, to each group appearance stimulation in various degree in the 5th day.The tetanic stimulation shape appears in the ear edge of finding former Elemenum Emulsion group in the process of administration.The degree that improved preparation occurred is very light.
Pathological observation: each is organized the ear edge and divides equally 6 sections observations.Though have similar vascular stimulation symptom to former elemene emulsion injection, the stimulation degree is lighter, and does not see thrombosis for elemene fat emulsion injection (vein is used); And it is little stimulating the also more former elemene emulsion injection of scope that takes place.
Annotate: this experiment is to carry out on the basis of above two kinds of experiments, has therefore only selected for use one 10% elemene fat emulsion injection (vein with) to compare.
Pharmacology irritant test conclusion: three prescription elemene fat emulsion injections (vein is used) cause pain and cause the test that stimulates model to carry out 3 kinds of selected animals, can reflect that all the more former elemene emulsion injection of newly-designed elemene fat emulsion transfusion all can ease the pain and vascular stimulation significantly.
It is as follows that elemene fat emulsion injection antineoplastic agent effect of the present invention is learned result of the test: the antitumor drug effect:
1, cell in vitro poison test: the outer inhibited proliferation of elemene fat emulsion injecting fluid, its IC to tumor cell lines such as human hepatoma cell strain QGY, lung cancer cell line LAX, breast carcinoma cell strain Bre-04, colon-cancer cell strain Col-06 and leukemia
50Value is between 60-120ug/ml.
2, anti-tumor in vivo test: the therapeutic scheme with 80mg/kg, 40mg/kg and high, medium and low three the dosage iv * 10qd of 20mg/kg in the elemene fat emulsion injecting fluid is respectively the tumour inhibiting rate of human hepatocellular QGY xenotransplantation in nude mouse subcutaneous vaccination model: 44.90%, 35.71% and 31.12%; The tumour inhibiting rate of Human Gastric Cancer MKN-45 xenotransplantation in nude mouse subcutaneous vaccination model is respectively: 41.70%, 32.26% and 26.42%; Tumour inhibiting rate to the artificial lung metastasis model of murine melanoma K111 intravenous inoculation is respectively: 56.28%, 48.38% and 42.91%; Prolongation vital rates to mouse brain glioma G-422 intracranial inoculation model is respectively: 68.23%, 55.29% and 49.41% and the tumour inhibiting rate of mouse brain glioma G422 subcutaneous vaccination model is respectively: 35.16%, 30.59% and 23.29%.
3, merge the antitumor curative effect of different chemotherapeutic to various mouse tumor models in the elemene fat emulsion injecting fluid: the therapeutic scheme of elemene fat emulsion injection employing 80mg/kg, 40mg/kg and the independent medication of high, medium and low three the dosage iv * 10qd of 20mg/kg is respectively the tumour inhibiting rate of murine sarcoma S180 subcutaneous vaccination model: 37.14%, 33.02% and 28.25%, merge CTX 15 mg/kg, the tumour inhibiting rate behind ip * 7qd rises to: 55.24%, 52.06% and 49.84%; Merge MMC 1mg/kg, the tumour inhibiting rate behind ip * 7qd rises to from 38.13%, 33.11%, 28.09% of independent medication respectively: 55.18%, 53.18% and 51.51%; Mouse brain glioma G-422 intracranial inoculation model is merged VM-26mg/kg, and the increase in life span behind ip * 7qd rises to from 60.60%, 41.41%, 32.32% of independent medication respectively: 92.93%, 83.84% and 73.74%; Mice Bearing Lewis Lung Cancer subcutaneous vaccination model is merged DDP 1mg/kg, rise to from 32.06%, 28.63%, 25.19% of independent medication respectively behind ip * 7qd: 54.96%, 52.67% and 51.15%; Artificial lung metastasis model to murine melanoma K111 intravenous inoculation merges DDP 1mg/kg, and the lung metastasis inhibition rate behind ip * 7qd rises to from 54.20%, 44.14%, 38.89% of independent medication: 58.36%, 55.56% and 53.86%.Merging different chemotherapeutic in the elemene fat emulsion injecting fluid all has in various degree raising to the antitumor curative effect of various mouse tumor models, and it is the most obvious wherein to merge the effect of VM-26 with mouse brain glioma G-422 intracranial inoculation model.
4, merge the tumour inhibiting rate of radiotherapy to rat liver cancer model in the elemene fat emulsion injecting fluid: the therapeutic scheme of elemene fat emulsion injection employing 80mg/kg, 40mg/kg and the independent medication of high, medium and low three the dosage iv * 10qd of 20mg/kg is respectively the tumour inhibiting rate of rat liver cancer H22 subcutaneous vaccination model: 37.97%, 33.62% and 26.96%, and the tumour inhibiting rate after merging radiotherapy 500 rads rises to: 61.16%, 59.71% and 60.00%;
5, immunologic function test: in the elemene fat emulsion injecting fluid with 80mg/kg, 40mg/kg and high, medium and low three the dosage iv * 10qd administrations of 20mg/kg to lotus Lewis lung cancer mice NK, lymphocyte proliferation activity, and normal Turnover of Mouse Peritoneal Macrophages phagocytic function all had significantly promote and improve.
6, attenuation test: the elemene fat emulsion injection is similar to positive control polysaccharide-peptide group to the leukocyte influence of C57BL/6 mice due to the CTX, influences not obviously, but does not also increase the bone marrow depression of chemotherapeutic.
The mice mtd test:
Maximum tolerated dose to the kunming mice intravenously administrable is 40mg/Kg, is 3～5 times of clinical dosage every day (400～700mg/50Kg/ time).
Vein local excitation test
Experimental result shows: when the elemene fat emulsion injection is applied to intravenous injection, rabbit auricular vein vascular stimulation is tested, dosage with stock solution 1mg/ml/Kg concentration, once a day, after continuous three days, experiment shows that elemene emulsion injection does not have the significantly irritant reaction relevant with medicine to tame rabbit ear vein blood vessel.
Hypersensitive test
Experimental result shows: elemene emulsion injection is not seen obvious anaphylaxis in the Cavia porcellus hypersensitive test.
Hemolytic test
Experimental result shows: elemene emulsion injection is to the reaction that is negative of rabbit erythrocyte hemolytic test.
Another object of the present invention has provided the preparation method of above-mentioned elemene fat emulsion injection, and this method is under inert gas shielding, and injection egg yolk lecithin (or injection soybean phospholipid) and elemene high-speed stirred are extremely evenly made oil phase.In addition glycerol for injection is added and fill in an amount of water for injection container, the mixing after-filtration is to clear and bright, be heated to 40～70 ℃ and make water, under high-speed stirred that oil phase is mixed with water and regulate pH value 8.0～10.0 with 10% sodium hydroxide solution, add to the full amount of water for injection colostrum is gone on foot the high pressure homogenization machines extremely newborn grain passed examination of emulsifying (particle＜account for more than 97% below 1 μ repeatedly through two, again through the filtering with microporous membrane fill in 250～500ml glass bottle, add logical nitrogen, plug, roll and be placed in the swinging steam autoclave 115 ℃ of sterilizations in 30 fens.After the passed examination the elemene fat emulsion injection.
The quality of the pharmaceutical preparations of the present invention is as follows:
1, character: this product is the emulsion liquid of white.
2, differentiate:
Get this product 3ml, put and add ethanol 1ml in the test tube, shake up the tailing edge tube wall and slowly add 1% vanillin sulphuric acid liquid 0.5ml,, shake up the back and show violet at two liquid layer intersection displaing amaranth rings.
In the chromatogram that writes down under the assay item, the retention time at test sample peak should be consistent with the retention time at reference substance peak.
3, inspection item: the every regulation under pH value, related substance, free fatty, breast grain size, pyrogen, the aseptic and relevant injection item.
4, assay: elemene adopts gas chromatography determination
5, related substance inspection: mainly check free fatty (employing chemical determination) and relative substance (employing gas chromatography determination).
6, stability test:
Elemene emulsion injection is through influence factor test (illumination, 40 ℃, 60 ℃, 80 ℃ quickened 10 days); 40 ℃ of constant temperature quickened after three months, and its content does not have significant change, and free-fat acid number and PH change to some extent along with time and temperature, and promptly PH has reduction slightly, and the free-fat acid number increases to some extent, but all can meet ordered quality standard.Other has no significant change as outward appearance, breast grain size etc., proves that tentatively this product can stablize about 2 years in the room temperature seasoning.
Formulation products of the present invention has following biological activity
1, suppress growth of tumour cell: body is interior, in vitro study shows that this product has effect to kinds of tumor cells.
2. immanoprotection action: this product can strengthen t lymphocyte subset group's function.
3. leukogenic effect: this product does not cause bone marrow depression, and leukocyte count does not have obvious decline during the medication, and the leukopenia that radiotherapy and other chemotherapeutic are caused has certain protective role.
4. to put. the chemotherapy synergism: this product and other chemotherapy drugs in combination are used (as cisplatin, etoposide, vincristine, amycin etc.) certain synergism.
5. Nutrition: this product is a lipid formulation, can provide high-energy and essential fatty acid nutritive for body.
6. can pass through blood brain barrier: the existence of blood brain barrier is a key factor that influences the intracranial tumor chemotherapy, the pharmacokinetics experiment of this product shows: the elemene through the 3H labelling can enter in the brain by blood brain barrier, its distribution and content are except that pulmonary is higher, and cerebral tissue is similar to its hetero-organization.The experimental oncology proof has higher prolongation vital rates with the mice of cerebroma in-situ inoculating.
The mechanism of action
1. directly suppress growth of tumour cell, less to normal cell (as peripheral blood leucocyte etc.) influence.
2. play the effect that suppresses cancerous protuberance by the human body immunity improving function.
3. act on cell cycle S phase and G
2And the check point of M phase, retardance S phase cell enters G
2+ M the phase, reduce tumor, cell division capacity suppresses its propagation.
4. by disturbing the growth of tumour cell metabolism, apoptosis takes place in induced tumor cell fast.
Toxicological effect
Anxious poison and long poison experimental results show that: this product toxic and side effects is humble.Intravenous LD
50Be 270.07 ± 18.93mg/kg; Mice there is not the teratogenesis mutation effect.Carried out long term toxicity test in continuous 90 days with Canis familiaris L. and rat vein administration, biochemical indicators such as hemogram of the various animals of result and liver, renal function have no significant change.
Indication
Mainly be applicable to pulmonary carcinoma, the brain cancer, hepatocarcinoma, gastric cancer etc.
Usage and consumption
Intravenous injection: every day 1 time, 400-600mg/ time, it is a course of treatment that vein slowly instiled 15 days.Choose thick vein blood vessel, two arms are used alternatingly, and preferably use the trocar.If can adopt the subclavian vein injection best.
The specific embodiment:
Embodiment one:
Under nitrogen protection, take by weighing injection soybean oil 120g, be heated to 70 ℃, add injection Ovum Gallus domesticus Flavus lecithin 13g and elemene 0.8g, high-speed stirred is made oil phase to evenly.In addition with glycerol for injection 23g, under high-speed stirred, be mixed and made into colostrum after adding ℃ filtration of an amount of water for injection mixing post-heating to 60 with oil phase, regulate pH value 9.5 with 10% sodium hydroxide solution then, add the injection water to 1000ml with colostrum through two step high pressure homogenization machines repeatedly emulsifying to breast grain passed examination (particle＜account for more than 97% below 1 μ), again through filtering with microporous membrane, fill logical nitrogen, is jumped a queue, is rolled and be placed on 115 ℃ of sterilizations in 30 fens in the swinging steam autoclave in 250～500ml glass bottle.After the passed examination the elemene fat emulsion injection.
Embodiment two:
Under nitrogen protection, take by weighing injection soybean oil 200g, be heated to 60 ℃, add elemene 1.5g, high-speed stirred is made oil phase to evenly.In addition glycerol for injection 22g is added and under high-speed stirred, add injection soybean phospholipid 8g mixing post-heating to 70 ℃ behind an amount of water for injection mixing again, under high-speed stirred, be mixed and made into colostrum with oil phase, and regulate pH value 8.5 with 10% sodium hydroxide solution, the 1000ml that adds to the full amount of water for injection goes on foot the high pressure homogenization machines extremely newborn grain passed examination (particle＜account for more than 97% below 1 μ) of emulsifying repeatedly with colostrum through two, again through the filtering with microporous membrane fill in 250～500ml glass bottle, logical nitrogen, jump a queue, roll and be placed on 115 ℃ of sterilizations in 30 fens in the swinging steam autoclave.After the passed examination the elemene fat emulsion injection.
Embodiment three:
Under nitrogen protection, take by weighing injection soybean oil 150g, be heated to 80 ℃, add injection Ovum Gallus domesticus Flavus lecithin 14g and elemene 1.2g, high-speed stirred is made oil phase to evenly.In addition with glycerol for injection 24g, under high-speed stirred, be mixed and made into colostrum after adding ℃ filtration of an amount of water for injection mixing post-heating to 50 with oil phase, regulate pH value 8.5 with 10% sodium hydroxide solution then, add the injection water to 1000ml with colostrum through two step high pressure homogenization machines repeatedly emulsifying to breast grain passed examination (particle＜below 1 μ, again through the filtering with microporous membrane fill in 250～500ml glass bottle, logical nitrogen, jump a queue, roll and be placed on 115 ℃ of sterilizations in 30 fens in the swinging steam autoclave.After the passed examination the elemene fat emulsion injection.
Claims (2)
1, a kind of elemene fat emulsion injection, the weight/volume % (g/ml) that it is characterized in that this injection consist of elemene 0.05～0.25%, injection soybean oil 10～30%, phospholipid and select injection Ovum Gallus domesticus Flavus lecithin 1.0～1.5% or injection soybean phospholipid 0.8～1.5%, glycerol for injection 2.0～2.5%, water for injection to add to 100ml.
2; a kind of preparation method of a kind of elemene fat emulsion injection as claimed in claim 1; it is characterized in that this method is under inert gas shielding; injection phospholipid and elemene high-speed stirred are extremely evenly made oil phase; in addition glycerol for injection is added and fill in an amount of water for injection container; the mixing after-filtration is to clear and bright; be heated to 40～70 ℃ and make water; under high-speed stirred, the oil phase colostrum of making mixed with water is also regulated pH value 8.0～10.0 with 10% sodium hydroxide solution; add to the full amount of water for injection colostrum is gone on foot the high pressure homogenization machines extremely newborn grain passed examination of emulsifying repeatedly through two; particle＜account for more than 97% below 1 μ; again through filtering with microporous membrane; fill is in 250～500ml glass bottle; logical nitrogen; add plug; roll and be placed in the swinging steam autoclave 115 ℃ of sterilizations in 30 fens, after the passed examination the elemene fat emulsion injection.
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| CN101810593B (en) | 2010-05-10 | 2012-07-18 | 谢恬 | Elemene sustained-release tablets |
| EP4070786A4 (en) * | 2019-12-03 | 2023-12-27 | Sichuan Honghe Biotechnology Co., Ltd | Pharmaceutical composition containing elemene, preparation method therefor, and use thereof |
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Address after: No. 1320 West Beijing Road, Shanghai, China: 200040 Co-patentee after: Dalian Hualide Pharmaceutical Co., Ltd. Patentee after: Shanghai Institute of pharmaceutical industry Address before: No. 1320 West Beijing Road, Shanghai, China: 200040 Co-patentee before: Dalian Deze Pharmaceutical Co. Ltd. Patentee before: Shanghai Institute of pharmaceutical industry |
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