CN1602865A - Fat emulsion injection of bulleyaconitine A and its manufacturing method - Google Patents
Fat emulsion injection of bulleyaconitine A and its manufacturing method Download PDFInfo
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- CN1602865A CN1602865A CN 03134916 CN03134916A CN1602865A CN 1602865 A CN1602865 A CN 1602865A CN 03134916 CN03134916 CN 03134916 CN 03134916 A CN03134916 A CN 03134916A CN 1602865 A CN1602865 A CN 1602865A
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Abstract
The invention provides a bulleyaconitine fat emulsion transfusion and its producing method, including effective component, medicinal auxiliary and emulsifier, and its characteristic: it uses bulleyaconitine as the effective component, contains 0.1-0.8mg of bulleyaconitine per bottle, and mixes in a proper amount of medicinal auxiliary and emulsifier to prepare the medicinally acceptable fat emulsion. At normal temperature, the emulsion can be placed for 1 year, stable and reliable, and through stimulative test on big white rabbits, the stimulative property of the emulsion is grade 0-1 and has better antiphlogistic and analgesic effect and energy supplementing effect and simultaneously, quickly takes effect and has good compliance of patient.
Description
Technical field
The present invention relates to a kind of bulleyaconitine A fat milk transfusion and production method thereof, belong to the production and the processing of pharmaceutical preparation.
Background technology
Bulk capacity injection (being called for short transfusion) is one of dosage form of comparatively commonly used and outbalance.It plays important role in severe crisis patient's treatment.Along with medical technology and expanding economy, medical department also improves constantly the requirement of transfusion.Country such as American and Britain is in the thirties in 20th century, and the high-octane infatmul agent that begins one's study just formally provides the fat milk of used for intravenous injection to supply clinical practice up to nineteen fifty-seven Upjohn company.China produces fat milk since 1980 in the mode of introducing.But Jue Dabufen fat milk transfusion can only use as the nutritional support agent so far, can not use as the curative effect-type preparation.Bulleyaconitine A is all to draw the new alkaloids of separating (Aconitum BulleyanumDiels) from Ranunculaceae aconitum plant the western regions of the Yunnan Province---alkali first (Bulleyaconitine A) is all drawn in the western regions of the Yunnan Province, according to existing report, it also can obtain from other plant, can also make with semisynthetic method.The preparation of bulleyaconitine A has injection, tablet, oral liquid, soft capsule at present.Exploitation is injection the earliest, clinically to rheumatic arthritis, rheumatoid arthritis, lumbar muscle strain, scapulohumeral periarthritis, extremity sprain, disease such as contusion has curative effect preferably.Also can be used for the pain that cancer, operation etc. produce in addition; For herpes zoster etc. certain curative effect is arranged.Because the water insoluble and easy decomposition of bulleyaconitine A, so when being made into injection, have to use organic solvents such as ethanol or propylene glycol, generation has an intense pain and defective such as injection site redness when causing injecting, and has had a strong impact on the range of application of said preparation.The patent No. is 93119545.4 Chinese patent, discloses ' aconitum kusnezoffii oral dosage form ', and the patent No. is another Chinese patent of 98106595.3, discloses ' radix aconiti kunsezoffii nail element soft capsule and production method thereof '.Above-mentioned oral formulations exists onset to reach the defective of patient dependence difference such as mouth fiber crops when oral slowly.Therefore, existing pharmaceutical preparation can't satisfy to the severe crisis patient implement fast, the demand of effective treatment.
Summary of the invention
The purpose of this invention is to provide a kind of steady quality, and anti-inflammatory analgesic and energy supplement the bulleyaconitine A fat milk transfusion and the production method thereof that unite two into one.
The present invention realizes by following technical proposal:
Described bulleyaconitine A fat milk transfusion, comprise effective ingredient, pharmaceutic adjuvant and emulsifying agent, it is characterized in that with the bulleyaconitine A being effective ingredient, and every bottle of transfusion contains bulleyaconitine A 0.1～0.8mg, is equipped with an amount of pharmaceutic adjuvant and emulsifying agent and makes pharmaceutically acceptable fat milk transfusion.
Described pharmaceutic adjuvant is for providing the fatty acid or derivatives thereof of high energy, the fatty acid or derivatives thereof is one or more in satisfied fatty acid or unsaturated fatty acid or the essential fatty acid, specifically is soybean oil, Oleum Arachidis hypogaeae semen, the refine Testa oryzae oil, Semen Tritici aestivi germ oil, Oleum sesami, Oleum Gossypii semen, Radix Oenotherae erythrosepalae oil, perilla oil, Oleum Hippophae, safflower oil, Semen Lini oil, Semen Maydis oil, Oleum Vitis viniferae, sand sagebrush seed oil, Princepia utilis oil, bathypelagic fish oil, oleic acid, Palmic acid, stearic acid, linoleic acid, alpha-linolenic acid, gamma-Linolenic acid, polyunsaturated fatty acid, eicosapentaenoic acid and ester thereof, docosahexenoic acid and ester thereof, a kind of or youngster's kind in the glycerol.
Described emulsifying agent is one or more in lecithin, cephalin, soybean phospholipid, xanthan gum, sucrose ester, low methoxyl pectin, arabic gum, ginsenoside, Radix Panacis Quinquefolii saponin, arasaponin, the blue saponin of strand fruit.
In the described bulleyaconitine A fat milk transfusion, other nutrients or the healing potion that can add some emulsifyings that do not influence fat and stability as required, specifically be in the aminoacid such as aspartic acid, arginine one or more, and in the trace element such as calcium chloride, potassium chloride, zinc sulfate, manganese sulfate one or more.
In the process of research bulleyaconitine A fat milk transfusion, solved a following difficult problem:
Because water insoluble, the easy decomposition of bulleyaconitine A, and the content in medicine is quite few again, and therefore, allow it dissolve fully and be evenly distributed in the pharmaceutical preparation is to be difficult to grasp.With organic solvents such as ethanol of the prior art or propylene glycol, then can not be prepared into heavy dose of infusion solution, otherwise the patient is unacceptable.We have carried out scrutiny and discussion to the performance of bulleyaconitine A, finally having obtained first bulleyaconitine A with trace is dissolved in the fat solvent, and then Radix Aconiti Kusnezoffii first placental extract grease by over and medicinal emulsifier made fat milk transfusion with existing processing technique, thereby improve the performance of complying with of this pharmaceutical preparation, the patient can be accepted.
The production method of bulleyaconitine A fat milk transfusion provided by the invention may further comprise the steps:
1, bulleyaconitine A is dissolved in the oils and fats of pharmaceutic adjuvant, and notes it is dissolved fully;
2, with emulsifying agent in the water-soluble or oils and fats;
3, with after Radix Aconiti Kusnezoffii first placental extract grease by over and oil soluble emulsifier or the water-soluble emulsifier, be broken into thick breast in 50～80 ℃;
4, thick breast is cooled to rapidly below 20 ℃, further emulsifying again gets finely divided submicron emulsion (being fat milk);
5, regulate pH value, behind thick emulsion droplet of filtering and the fragment, the filtrate packing, Zha Gai gets the fat milk transfusion product;
6,, sterilized 15 minutes down at 121 ℃, or, cool off the preservation of shady and cool place gradually with the sterilization of rotation steriliser towards hot water with the preheating of gained preparation.
Above steps is all carried out under nitrogen protection, and the dosing process is carried out under 100 grades condition.
Bulleyaconitine A fat milk transfusion provided by the invention our experiments show that:
1, stability: the bulleyaconitine A fat milk transfusion was placed 1 year at normal temperatures, and product is reliable and stable, and every index is all qualified, meets the requirement of injection fully.
2, blood vessel irritation test: do irritant experiment with White Rabbit, the zest of bulleyaconitine A fat milk transfusion is 0 ~ 1 grade, does not promptly have significant change or mild hyperaemia.
3, anti-inflammatory analgesic: aspect anti-inflammatory analgesic with the effect basically identical of bulleyaconitine A powder pin and bulleyaconitine A injection.
Provide specific embodiments of the invention below, but scope of the present invention is not limited thereto.
Embodiment 1
Prescription:
Bulleyaconitine A 0.1g soybean oil 7500g
Glycerol 1250g soybean phospholipid 750g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of glycerol, and notes it is dissolved fully.Under nitrogen protection, soybean phospholipid is joined in the water for injection of 20000ml, add bulleyaconitine A glycerin liquid and soybean oil again, add water for injection to 50000ml.In 70～80 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.1mg.
Embodiment 2
Prescription:
Bulleyaconitine A 0.2g safflower oil 6000g
Glycerol 1000g low fat pectin 700g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of safflower oil, and notes it is dissolved fully.Under nitrogen protection, low fat pectin is joined in the water for injection of 20000ml, add bulleyaconitine A Flos Carthami fluid and glycerol again, add water for injection to 50000ml.In 70～80 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.2mg.
Embodiment 3
Prescription:
Bulleyaconitine A 0.1g Oleum sesami 6500g
Radix Oenotherae erythrosepalae oil 1000g glycerol 1200g
Soybean phospholipid 700g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of glycerol, and notes it is dissolved fully.Under nitrogen protection, soybean phospholipid is joined in the water for injection of 20000ml, add bulleyaconitine A glycerin liquid and Radix Oenotherae erythrosepalae oil again, Oleum sesami is added water for injection to 50000ml.In 70～80 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.1mg.
Embodiment 4
Prescription:
Bulleyaconitine A 0.4g soybean oil 7500g
Gamma-Linolenic acid 1000g glycerol 1250g
Soybean phospholipid 750g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of soybean oil, and notes it is dissolved fully.Under nitrogen protection, soybean phospholipid is joined in the water for injection of 20000ml, add bulleyaconitine A Semen sojae atricolor fluid, glycerol, gamma-Linolenic acid again, add water for injection to 50000ml.In 60～70 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.4mg.
Embodiment 5
Prescription:
Bulleyaconitine A 0.6g soybean oil 500g
Docosahexenoic acid and ester 500g vitamin E 100g thereof
Glycerol 1250g lecithin 650g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of glycerol, and notes it is dissolved fully.Under nitrogen protection, lecithin is joined water for injection, add bulleyaconitine A glycerin liquid, soybean oil, docosahexaenoic acid ethyl again, add water for injection to 50000ml.In 55～60 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, packing, check, qualified, finished product.Can make the bulleyaconitine A fat milk transfusion finished product of the specification of 1000 bottles of 50ml: 0.6mg.
Embodiment 6
Prescription:
Bulleyaconitine A 0.2g soybean oil 500g
Oleum Hippophae 600g glycerol 1250g
Cephalin 650g Radix Notoginseng total arasaponins 100g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of glycerol, and notes it is dissolved fully.Under nitrogen protection, cephalin, Radix Notoginseng total arasaponins are joined in the water for injection of 20000ml, add bulleyaconitine A glycerin liquid and soybean oil and Oleum Hippophae again, add water for injection to 50000ml.In 70～75 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.2mg.
Embodiment 7
Prescription:
Bulleyaconitine A 0.8g soybean oil 7500g
Glycerol 1250g soybean phospholipid 750g
Eight kinds of essential amino acids mixture 400g
Preparation technology: under 100 grades condition, bulleyaconitine A is dissolved in earlier in an amount of glycerol, and notes it is dissolved fully.Under nitrogen protection, soybean phospholipid and eight kinds of essential amino acids mixture are joined in the water for injection of 20000ml, add bulleyaconitine A glycerin liquid and soybean oil again, add water for injection to 50000ml.In 70～80 ℃ with organizing beating crusher to make thick breast.Thick breast is cooled to rapidly below 20 ℃, and the high pressure dispersing emulsification machine emulsifying of two step of reuse promptly gets finely divided submicron emulsion (fat milk).Filter with No. 4 sintered filter funnels, fine straining liquid is sent into racking machine, by every bottle of 50ml packing, Zha Gai, pack, be up to the standards, the bulleyaconitine A fat milk transfusion finished product of specification of 1000 bottles of 50ml: 0.8mg.
Bulleyaconitine A fat milk transfusion provided by the invention, through pharmacy, pharmacodynamic study, the result is as follows:
1, bulleyaconitine A fat milk transfusion stability test:
Assay and discriminating etc. are concentrated the bulleyaconitine A injection with reference to Yunnan Province's drug standard in 1996 in the quality standard.The result is as follows:
| Sample | Sample size, discriminating |
| 6 months March of 2 month January December | |
| The qualified qualified example of the qualified qualified example of example 123 is qualified slightly falls example 4 qualified qualified example 5 qualified qualified example 6 qualified qualified example 7 qualified qualified content and slightly descends and slightly fall | |
The result shows the sample of this invention preparation, and through the preliminarily stabilised investigation, product quality is basicly stable, can reach more than 1 year.
2, the analgesic activity of bulleyaconitine A fat milk transfusion
Mouse writhing method:
30 of mices are divided into 3 groups at random, and 10 every group, 20min behind the drug administration by injection, mouse peritoneal inject 0.7% acetic acid 0.1ml/10g, and record 5～15min mouse writhing reaction times is calculated and comparable group differences significance, the results are shown in following table:
Group body weight dosage (mg/Kg) is turned round body number of times suppression ratio
Blank group 20 ± 1.0 equal-volumes 30.8 ± 8.02
Morphine group 20 ± 1.2 10 2.5 ± 1.55 92.1%
Transfusion group 20 ± 1.1 4ml/ only 19.9 ± 6.72 42.4%
The result shows that the bulleyaconitine A fat milk transfusion has significant analgesia role.
3, the antiinflammatory action of bulleyaconitine A fat milk transfusion
Use the Whttle method, 30 of mices are divided into 3 groups at random, 10 every group, 20min behind the drug administration by injection, the blue 0.2ml/ of mouse tail vein injection 0.5% ivens is the timely lumbar injection 0.7% acetic acid 0.2ml/10g in back only, puts to death mice behind the 15min, and intraperitoneal injection of saline 5ml gently rubs the back and extracts peritoneal fluid, centrifugal, supernatant is measured optical density value in the 620nm place, calculate and comparable group differences significance, the results are shown in following table:
Group body weight dosage (mg/Kg) optical density value suppression ratio
Blank group 20 ± 1.1 equal-volumes 0.27 ± 0.05
A department woods 20 ± 1.1 200 0.13 ± 0.02 60.5%
Transfusion group 20 ± 1.3 4ml/ only 0.17 ± 0.03 49.4%
The result shows that the bulleyaconitine A fat milk transfusion has certain anti-inflammatory activity.
4, the irritation test of bulleyaconitine A fat milk transfusion
Get 4 of healthy rabbits, W:2.0～2.2kg, male and female half and half, be divided into two groups, inject bulleyaconitine A fat milk transfusion 1ml (embodiment 5) respectively on its left and right sides lower limb quadriceps femoris, 48h puts to death rabbit behind the medicine, cuts open the inspection quadriceps femoris, vertically cut and observe injection site muscular irritation reaction, and according to the form below converses corresponding order of reaction.
Local muscular irritation order of reaction table:
The order of reaction irritant reaction
0 no significant change
1 mild hyperaemia, its scope is less than 0.5～1.0cm
2 moderate hyperemia, its scope is less than 0.5～1.0cm
3 severe hyperemia are with myodegeneration
4 necrosis occurs, and the brown degeneration is arranged
5 the popularity necrosis occurs
The result: the zest of bulleyaconitine A fat milk transfusion is 0 grade, i.e. nonirritant.
Claims (6)
1, a kind of bulleyaconitine A fat milk transfusion, comprise effective ingredient, pharmaceutic adjuvant and emulsifying agent, it is characterized in that with the bulleyaconitine A being effective ingredient, and every bottle of transfusion contains bulleyaconitine A 0.1～0.8mg, is equipped with an amount of pharmaceutic adjuvant and emulsifying agent and makes pharmaceutically acceptable fat milk transfusion.
2, bulleyaconitine A fat milk transfusion according to claim 1, it is characterized in that described pharmaceutic adjuvant is for providing the fatty acid or derivatives thereof of high energy, the fatty acid or derivatives thereof is one or more in satisfied fatty acid or unsaturated fatty acid or the essential fatty acid, specifically is soybean oil, Oleum Arachidis hypogaeae semen, the refine Testa oryzae oil, Semen Tritici aestivi germ oil, Oleum sesami, Oleum Gossypii semen, Radix Oenotherae erythrosepalae oil, perilla oil, Oleum Hippophae, safflower oil, Semen Lini oil, Semen Maydis oil, Oleum Vitis viniferae, sand sagebrush seed oil, Princepia utilis oil, bathypelagic fish oil, oleic acid, Palmic acid, stearic acid, linoleic acid, alpha-linolenic acid, gamma-Linolenic acid, polyunsaturated fatty acid, eicosapentaenoic acid and ester thereof, docosahexenoic acid and ester thereof, in the glycerol one or more.
3, bulleyaconitine A fat milk transfusion according to claim 1 is characterized in that described emulsifying agent is one or more in lecithin, cephalin, soybean phospholipid, xanthan gum, sucrose ester, low methoxyl pectin, arabic gum, ginsenoside, Radix Panacis Quinquefolii saponin, arasaponin, the blue saponin of strand fruit.
4, the plain fat milk transfusion of mare first according to claim 1, it is characterized in that in the described bulleyaconitine A fat milk transfusion, other nutrients or the healing potion that can add some emulsifyings that do not influence fat and stability as required, specifically be in the aminoacid such as aspartic acid, arginine one or more, and in the trace element such as calcium chloride, potassium chloride, zinc sulfate, manganese sulfate one or more.
5, the production method of bulleyaconitine A fat milk transfusion is characterized in that may further comprise the steps:
A, bulleyaconitine A are dissolved in the oils and fats of pharmaceutic adjuvant, and note it is dissolved fully;
B, with emulsifying agent in the water-soluble or oils and fats;
C, with after Radix Aconiti Kusnezoffii first placental extract grease by over and oil soluble emulsifier or the water-soluble emulsifier, be broken into thick breast in 50～80 ℃;
D, thick breast is cooled to rapidly below 20 ℃, further emulsifying again, finely divided submicron emulsion (being fat milk);
E, adjusting pH value, behind thick emulsion droplet of filtering and the fragment, the filtrate packing, Zha Gai gets the fat milk transfusion product;
F, with the preheating of gained preparation, 121 ℃ of down sterilizations 15 minutes, or, cool off the preservation of shady and cool place gradually with the sterilization of rotation steriliser towards hot water.
6, the production method of bulleyaconitine A fat milk transfusion according to claim 5 is characterized in that above steps all carries out under nitrogen protection, the dosing process is carried out under 100 grades condition.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100518721C (en) * | 2006-08-08 | 2009-07-29 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets containing aconitine, and preparation method thereof |
| CN101040853B (en) * | 2006-03-22 | 2010-05-12 | 上海医药工业研究院 | A kind of aconitin multivesicular liposome and preparation method thereof |
| CN101057845B (en) * | 2006-04-17 | 2012-03-21 | 陈云生 | Bulleyaconitin A dry emulsion and its preparation method and application |
| CN105287674A (en) * | 2015-11-23 | 2016-02-03 | 青岛麦瑞特医药技术有限公司 | Pain-relieving liniment used for treating degenerative osteoarthropathy or muscle injury |
| CN105832744A (en) * | 2016-05-17 | 2016-08-10 | 海南合瑞制药股份有限公司 | Alprostadil freeze-dried emulsion composition for injection |
| WO2021143751A1 (en) * | 2020-01-14 | 2021-07-22 | 中国科学院上海药物研究所 | Injectable long-acting analgesic pharmaceutical composition, preparation method therefor, and application thereof |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| IL88076A (en) * | 1987-10-28 | 1993-01-14 | Nippon Shinyaku Co Ltd | Fat emulsions as drug carriers |
-
2003
- 2003-09-30 CN CNB031349161A patent/CN1297271C/en not_active Expired - Fee Related
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101040853B (en) * | 2006-03-22 | 2010-05-12 | 上海医药工业研究院 | A kind of aconitin multivesicular liposome and preparation method thereof |
| CN101057845B (en) * | 2006-04-17 | 2012-03-21 | 陈云生 | Bulleyaconitin A dry emulsion and its preparation method and application |
| CN100518721C (en) * | 2006-08-08 | 2009-07-29 | 云南昊邦制药有限公司 | Enteric quick-dissolving tablets containing aconitine, and preparation method thereof |
| CN105287674A (en) * | 2015-11-23 | 2016-02-03 | 青岛麦瑞特医药技术有限公司 | Pain-relieving liniment used for treating degenerative osteoarthropathy or muscle injury |
| CN105832744A (en) * | 2016-05-17 | 2016-08-10 | 海南合瑞制药股份有限公司 | Alprostadil freeze-dried emulsion composition for injection |
| CN105832744B (en) * | 2016-05-17 | 2018-10-30 | 浙江长典医药有限公司 | A kind of Alprostadil freeze-dried emulsion composition of injection |
| WO2021143751A1 (en) * | 2020-01-14 | 2021-07-22 | 中国科学院上海药物研究所 | Injectable long-acting analgesic pharmaceutical composition, preparation method therefor, and application thereof |
| CN114980890A (en) * | 2020-01-14 | 2022-08-30 | 中国科学院上海药物研究所 | Injectable long-acting analgesic pharmaceutical composition and preparation method and application thereof |
| CN114980890B (en) * | 2020-01-14 | 2024-05-31 | 中国科学院上海药物研究所 | Injectable long-acting analgesic drug composition and preparation method and use thereof |
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