CN108653208A - A kind of alprostadil injection - Google Patents
A kind of alprostadil injection Download PDFInfo
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- CN108653208A CN108653208A CN201710205881.4A CN201710205881A CN108653208A CN 108653208 A CN108653208 A CN 108653208A CN 201710205881 A CN201710205881 A CN 201710205881A CN 108653208 A CN108653208 A CN 108653208A
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
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- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
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- A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
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- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
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Abstract
The present invention provides a kind of alprostadil injection, and containing Alprostadil, phosphatide, oil for injection and water for injection, each component content is：Alprostadil 48 μ g/ml, phosphatidase 4 20mg/ml, 100 300mg/ml of oil for injection, wherein include phosphatidyl choline PC, phosphatidyl glycerol PG and PC in phosphatide:PG is 95:5~99.7:0.3, also include the tocopherol for accounting for phosphatide total amount and being 0.02% 0.5% in phosphatide.Alprostadil injection provided by the invention has good compatibility stability with octreotide acetate injection, and has been surprisingly found that, alprostadil injection prepared by the present invention can significantly reduce blood vessel irritation and reduce injection pain.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, and in particular to a kind of alprostadil injection.
Background technology
Alprostadil, also known as prostaglandin E1 (PGE1) are a kind of physiological activators that activity is extremely strong, have and inhibit blood
Platelet aggregation, thromboxane A2 generate, the athero- Lipid Plaque of artery is formed and the effect of immune complex, and can expand periphery and hat
The pharmacological action of arteries and veins blood vessel is mainly used for treating chronic arterial occlusion disease (Buerger's disease, Arteriosclerosis obliterans
Deng) caused by four control four limbs tranquillization pain caused by ulcer and tiny blood vessels dyshaemia, improve cardiovascular and cerebrovascular microcirculation disorder
And the auxiliary treatment of chronic hepatitis.
The Alprostadil preparation listed at present has Alprostadil powder needle (cyclodextrin inclusion compound) and alprostadil injection (fat
Fat emulsion formulation).Alprostadil chemical property is unstable, is metabolized in vivo quickly, in order to improve its stability, by powder-injection into one
Step exploitation is using the alprostadil injection of lipid microspheres drug delivery technologies.Lipid microspheres are one kind using fat oil as soft base matter, phosphatide
For emulsifier microsome dispersion, preparation method is that drug is dissolved in fat oil, using refined lecithin as emulsifier, warp
It is high-pressure homogeneous at O/W type drug-loaded emulsions.
Acute pancreatitis is the relatively conventional acute disease of internal medicine, since enzymatic activity enhancing easily occurs pancreatic tissue itself
The systemic inflammatoromes such as oedema, digestion or hemorrhagic necrosis, incidence is in significantly raised trend, case fatality rate 10%-15% in recent years.
Clinic is united and applied in the treatment of acute pancreatitis frequently with Octreotide and Alprostadil at present, clinically there is good treatment
Effect.Since alprostadil injection is fat emulsion injection, key technical index such as average grain diameter and catabolite PGA1
Its Clinical practice effect can be affected greatly.But have in the prior art with octreotide acetate injection without one kind
The alprostadil injection of preferable compatibility stability.
For ease of being administered and improving compliance when patient clinical uses, it is necessary to provide a kind of be suitble to and Octreotide compatibility
Alprostadil injection.
Invention content
It is an object of the invention to overcome the deficiencies of existing technologies, provide one kind has with octreotide acetate injection compatibility
The alprostadil injection of better stability, has been surprisingly found that, alprostadil injection prepared by the present invention can significantly reduce blood
The generation of pipe irritation and injection pain.
The present invention provides a kind of alprostadil injection, containing Alprostadil, phosphatide, oil for injection and water for injection,
Each component content is：
Alprostadil 4-8 μ g/ml,
Phosphatidase 4-20mg/ml,
Oil for injection 100-300mg/ml,
Wherein, include phosphatidyl choline PC, phosphatidyl glycerol PG and PC in the phosphatide:PG is 95:5~99.7:
0.3, also include to account for the tocopherol that phosphatide total amount is 0.02%-0.5% in phosphatide.
In above-mentioned alprostadil injection, the PC:PG is 99:1~99.7:0.3.
In above-mentioned alprostadil injection, it is 0.1%-0.2% that the tocopherol, which accounts for phosphatide total amount,.
In above-mentioned alprostadil injection, a concentration of 5 μ g/ml of Alprostadil, a concentration of 18mg/ml of phosphatide, injection
With a concentration of 100mg/ml of oil.
In above-mentioned alprostadil injection, the phosphatidyl choline is selected from natural phosphatidyl choline and its salt,
Phosphatidyl choline and its salt of synthesis or combinations thereof；The phosphatidyl choline of the synthesis is selected from distearoyl phosphatidylcholine,
Dioleyl phosphatidyl choline, Dioctonoyl pnosphotidyl choline, L-Dimyristoylphosphatidylcholine, didecyl acyl phospholipids acyl
Choline, Dilauroyl Phosphatidylcholine, two mustard phosphatidyl cholines, 1- stearyl -2- oleolyl phosphatidyl cholines, 1-
Palmityl -2- oleolyl phosphatidyl cholines, 1- myristoyl -2- oleolyl phosphatidyl cholines, 1- stearyl -2- palms
Phosphatidyl choline, 1- stearyl -2- myristoyl phosphatidyl cholines, 1- palmityl -2- stearoyl phosphatidyls
Choline, 1- palmityl -2- myristoyl phosphatidyl cholines, 1- myristoyl -2- stearoyl phosphatidyl choline, 1- meat
Cardamom acyl group -2- palmityl phosphatidyl cholines or combinations thereof.
In above-mentioned alprostadil injection, the phosphatidyl glycerol is selected from natural phosphatidyl glycerol and its salt,
The phosphatidyl glycerol and its salt of synthesis or a combination thereof；It is sweet that the phosphatidyl glycerol of the synthesis is selected from distearyl acyl group phosphatidyl
Oil, dioleoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, dimyristoylphosphatidylglycerol, 1- palmityls-
2- oleolyl phosphatidyl glycerine, two mustard acyl phosphatidyl glycerols, dilauroylphosphatidylglycerol or combinations thereof.
In above-mentioned alprostadil injection, the oil for injection is selected from refined soybean oil, safflower oil, cottonseed oil, olive
Oil, coconut oil, castor oil, fish oil, medium chain mono, medium chain triglyceride dibasic acid esters, medium chain triglyceride, ethyl oleate, acetylation
Monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate, polyethylene glycol glyceryl laurate ester or combinations thereof.
In above-mentioned alprostadil injection, also include isotonic regulator, the isotonic regulator be selected from glycerine, glucose,
Mannitol or combinations thereof.
In above-mentioned alprostadil injection, also include pH adjusting agent, the pH adjusting agent be selected from sodium hydroxide, hydrochloric acid,
Phosphoric acid, phosphate, citric acid, citrate, acetic acid, acetate or combinations thereof.
A kind of preparation method preparing above-mentioned alprostadil injection, comprises the steps of：
(1) preparation of water phase：Glycerine is added in recipe quantity water for injection, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in oil for injection, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Specific implementation mode
Comparative example 1
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 16.184g, phosphatidyl glycerol 1.798g, tocopherol 18mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Comparative example 2
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.82g, phosphatidyl glycerol 0.18g in above-mentioned prescription, is free of tocopherol.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Comparative example 3
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Oleic acid | 2.4g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.982g, tocopherol 18mg in above-mentioned prescription, is free of phosphatidyl glycerol.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil, oleic acid are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 1
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.083g, phosphatidyl glycerol 0.899g, tocopherol 18mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 2
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.802g, phosphatidyl glycerol 0.18g, tocopherol 18mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 3
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.928g, phosphatidyl glycerol 0.054g, tocopherol 18mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 4
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.8164g, phosphatidyl glycerol 0.18g, tocopherol 3.6mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 5
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.784g, phosphatidyl glycerol 0.18g, tocopherol 36mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
Embodiment 6
| Prescription | Dosage |
| Alprostadil | 5mg |
| Phosphatide | 18g |
| Soybean oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 17.731g, phosphatidyl glycerol 0.179g, tocopherol 90mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in soybean oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
1 compatibility stability of test case is tested
Experimental drug：Octreotide acetate injection (Beijing Bai'ao Pharmaceutical Industry Co., Ltd.), embodiment 1-6 and comparative example
1-3 alprostadil injection samples.
Experimental method the sample of the sample of 1-6 of the embodiment of the present invention and comparative example 1-3 are taken respectively 1ml and 0.6mg (with
Octreotide meter) octreotide acetate injection and 100ml physiological saline carries out compatibility, places at room temperature, and it observes and detects items and refer to
Mark.The experimental results are shown inthe following table.
According to above-mentioned test result it can be found that the alprostadil injection for preparing of 1-6 of the embodiment of the present invention with acetic acid
Its content, average grain diameter and particle diameter distribution all maintain maintenance level when content of octreotide injection carries out compatibility, have good
Compatibility stability.Alprostadil injection prepared by comparative example 1 and comparative example 2 is when with content of octreotide injection compatibility, grain size point
Cloth changes greatly, and has exceeded quality standard regulation (particle diameter distribution should be less than 0.2).Alprostadil injection prepared by comparative example 3
Liquid is when with content of octreotide injection compatibility, although can ensure the stabilization of average grain diameter and particle diameter distribution, its content declines
It is very big.Alprostadil injection prepared by comparative example 1-3 can not carry out compatible use with content of octreotide injection.
2 vascular stimulation tests of test case
Rabbit 18, female, 2.0~2.4kg are divided into two groups, and every group 9, every left ear gives comparative example 1-3 and reality respectively
The alprostadil injection of a 1-6 is applied, auris dextra gives equal capacity 0.9% sodium chloride injection.Each ear is before injection with medical wine
After essence disinfection, in auricular vein away from inserting needle at tip about 1cm, tested material is slowly injected, is administered once a day, for three days on end.Every time
After administration and next time before administration observation injection site vein (blood vessel) and surrounding subcutaneous tissue and ear epidermis stimulate the reaction, make
Record in detail.It scores by the scoring of 1 blood vessel irritation of table and criterion.Animal was put to death in 24 hours after the last administration, is cut
Injection site auricular concha about 5cm long is taken, after being fixed with 10% formalin, inspection pathology.Finally comprehensive naked eyes and histological score
It is worth evaluation test result.
Observation injection site vein (blood vessel) and surrounding subcutaneous tissue and ear epidermis before administration after administration and next time every time
Stimulate the reaction, be showed no significant change.Pathological examination results also have no that blood vessel and surrounding tissue have significant change, are pierced by blood vessel
It is that the score of embodiment 1-6 is respectively less than 0.5, thus judges alprostadil injection under this invention to swash standards of grading cumulative score
Liquid vascular irritation；Comparative example 1, comparative example 2 and 3 groups of scores of comparative example are respectively 1.5,2,2, there is slight stimulation.
1 blood vessel irritation of table scores and criterion
3 rat of test case licks full test
Take SD rats 16, half male and half female, weight 200-250g.Rat is pressed into gender, weight equilibrium is randomly divided into 2 groups,
Every group 8, first group is in right hindpaw injection 2 alprostadil injection of the embodiment of the present invention (5 μ g/ml), the upper Chinese system of weights of second group injection
When agent is triumphant (5 μ g/ml), dosage is 0.1ml.The time is recorded after administration and is recorded licks for the first time in sufficient time and 10 minutes
Lick sufficient number.It counts every group to lick the sufficient time for the first time and lick the average of sufficient number, when result is that the embodiment of the present invention 2 licks sufficient for the first time
Between average be 20.2s, averagely lick sufficient number be 7.5 times；The sufficient time average of licking for the first time of listing preparation is 12.3s, average
It is 17.5 times to lick sufficient number.
It can be seen that alprostadil injection prepared by the embodiment of the present invention 2 licks the sufficient time compared to listing preparation for the first time
Delay, and sufficient number is licked less than more than half for listing preparation group.Alprostadil injection prepared by the present invention is noted
Penetrate pain degree significantly reduces compared to listing preparation.
Embodiment 7
| Prescription | Dosage |
| Alprostadil | 4mg |
| Phosphatide | 4g |
| Olive oil | 100g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 3.789g, phosphatidyl-ethanolamine 0.199g, tocopherol 12mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in olive oil, stirred to dissolve, as oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
After testing, the alprostadil injection indices obtained by embodiment 7 meet the requirements.
Embodiment 8
Phosphatide includes phosphatidyl choline 11.844g, phosphatidyl glycerol 0.12g, tocopherol 36mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in olive oil and medium chain triglyceride, stirred to dissolve,
As oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
After testing, the alprostadil injection indices obtained by embodiment 6 meet the requirements.
Embodiment 9
| Prescription | Dosage |
| Alprostadil | 8mg |
| Phosphatide | 20g |
| Olive oil | 150g |
| Medium chain triglyceride | 150g |
| Glycerine | 22.1g |
| 0.1M NaOH | In right amount |
Phosphatide includes phosphatidyl choline 19.85g, phosphatidyl glycerol 0.06g, tocopherol 90mg in above-mentioned prescription.
Preparation method：
(1) preparation of water phase：Glycerine is added to the water, is stirred to dissolve, as water phase；
(2) preparation of oil phase：Phosphatide, Alprostadil are added in olive oil and medium chain triglyceride, stirred to dissolve,
As oil phase；
(3) during the oil phase is added to the aqueous phase, it is 1000ml to make total amount, and high speed shear dispersion forms colostrum；
(4) colostrum is high-pressure homogenising, obtain smart breast；
(5) filling, sterilizing, thus obtaining the product.
After testing, the alprostadil injection indices obtained by embodiment 9 meet the requirements
The preferred embodiment of the present invention is described in detail in the above.But the present invention is not limited to above-mentioned embodiment party
Detail in formula can carry out a variety of simple changes to technical scheme of the present invention within the scope of the technical concept of the present invention
Type, these simple variants all belong to the scope of protection of the present invention.
It is further to note that specific technical features described in the above specific embodiments, in not lance
In the case of shield, it can be combined in any manner.In order to avoid unnecessary repetition, the present invention is to various possible groups
Conjunction mode no longer separately illustrates.
In addition, various embodiments of the present invention can be combined randomly, without departing from this hair
Bright thought, it should also be regarded as the disclosure of the present invention.
Claims (10)
1. a kind of alprostadil injection, containing Alprostadil, phosphatide, oil for injection and water for injection, each component content is：
Alprostadil 4-8 μ g/ml,
Phosphatidase 4-20mg/ml,
Oil for injection 100-300mg/ml,
It is characterized in that, including phosphatidyl choline PC, phosphatidyl glycerol PG and PC in the phosphatide:PG is 95: 5~
99.7 :0.3, also include to account for the tocopherol that phosphatide total amount is 0.02%-0.5% in phosphatide.
2. alprostadil injection according to claim 1, which is characterized in that the PC:PG is 99:1~99.7:
0.3。
3. according to any alprostadil injections of claim 1-2, which is characterized in that it is total that the tocopherol accounts for phosphatide
Amount is 0.1%-0.2%.
4. according to any alprostadil injections of claim 1-3, which is characterized in that the concentration of the Alprostadil
For 5 μ g/ml, a concentration of 18mg/ml of phosphatide, a concentration of 100mg/ml of oil for injection.
5. alprostadil injection according to claim 1, which is characterized in that the phosphatidyl choline is selected from natural next
The phosphatidyl choline and its salt in source, phosphatidyl choline and its salt of synthesis or combinations thereof；The phosphatidyl choline of the synthesis is selected from
Distearoyl phosphatidylcholine, dioleyl phosphatidyl choline, Dioctonoyl pnosphotidyl choline, two myristoyl phosphatide
Phatidylcholine, Dinonyl Phosphatidylcholine, Dilauroyl Phosphatidylcholine, two mustard phosphatidyl cholines, 1- stearyls-
2- oleolyl phosphatidyl cholines, 1- palmityl -2- oleolyl phosphatidyl cholines, 1- myristoyl -2- oleolyl phosphatidyls
Choline, 1- stearyl -2- palmityl phosphatidyl cholines, 1- stearyl -2- myristoyl phosphatidyl cholines, 1- palms
Acyl group -2- stearoyl phosphatidyl choline, 1- palmityl -2- myristoyl phosphatidyl cholines, 1- myristoyls -2- are hard
Fatty acyl group phosphatidyl choline, 1- myristoyl -2- palmityl phosphatidyl cholines or combinations thereof.
6. alprostadil injection according to claim 1, which is characterized in that the phosphatidyl glycerol is selected from natural next
The phosphatidyl glycerol and its salt in source, the phosphatidyl glycerol and its salt of synthesis or a combination thereof；The phosphatidyl glycerol of the synthesis selects
From distearoylphosphatidylglycerol, dioleoylphosphatidylglycerol, dipalmitoylphosphatidylglycerol, two myristoyl phosphorus
Phosphatidyl glycerol, 1- palmityl -2- oleolyl phosphatidyl glycerine, two mustard acyl phosphatidyl glycerols, dilauroylphosphatidylglycerol or
A combination thereof.
7. alprostadil injection according to claim 1, which is characterized in that the oil for injection is selected from Refined Soybean
Oil, safflower oil, cottonseed oil, olive oil, coconut oil, castor oil, fish oil, medium chain mono, medium chain triglyceride dibasic acid esters, medium chain triglyceride
Three esters, ethyl oleate, acetylated monoglyceride, propylene glycol dibasic acid esters, glyceryl linoleate, polyethylene glycol glyceryl laurate ester or its
Combination.
8. according to any alprostadil injections of claim 1-7, which is characterized in that also include isotonic regulator, institute
It states isotonic regulator and is selected from glycerine, glucose, mannitol or combinations thereof.
9. according to any alprostadil injections of claim 1-7, which is characterized in that also include pH adjusting agent, it is described
PH adjusting agent be selected from sodium hydroxide, hydrochloric acid, phosphoric acid, phosphate, citric acid, citrate, acetic acid, acetate or combinations thereof.
10. a kind of preparation method preparing any alprostadil injections of claim 1-9, comprises the steps of：
（1）The preparation of water phase：Glycerine is added in recipe quantity water for injection, is stirred to dissolve, as water phase；
（2）The preparation of oil phase：Phosphatide, Alprostadil are added in oil for injection, stirred to dissolve, as oil phase；
（3）During the oil phase is added to the aqueous phase, high speed shear dispersion forms colostrum；
（4）Colostrum is high-pressure homogenising, obtain smart breast；
（5）It is filling, sterilizing, thus obtaining the product.
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| CN201710205881.4A CN108653208A (en) | 2017-03-30 | 2017-03-30 | A kind of alprostadil injection |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201710205881.4A CN108653208A (en) | 2017-03-30 | 2017-03-30 | A kind of alprostadil injection |
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Citations (3)
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|---|---|---|---|---|
| CN101511367A (en) * | 2006-09-05 | 2009-08-19 | 丘比株式会社 | Prostaglandin fat emulsion, method for producing the same, method for stabilizing the same, and emulsifying agent |
| CN103536532A (en) * | 2013-10-25 | 2014-01-29 | 北京蓝丹医药科技有限公司 | Alprostadil composition as well as preparation method thereof |
| CN105012248A (en) * | 2014-04-29 | 2015-11-04 | 北京蓝丹医药科技有限公司 | Injection alprostadil fat emulsion and preparing method thereof |
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2017
- 2017-03-30 CN CN201710205881.4A patent/CN108653208A/en active Pending
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| CN101511367A (en) * | 2006-09-05 | 2009-08-19 | 丘比株式会社 | Prostaglandin fat emulsion, method for producing the same, method for stabilizing the same, and emulsifying agent |
| CN103536532A (en) * | 2013-10-25 | 2014-01-29 | 北京蓝丹医药科技有限公司 | Alprostadil composition as well as preparation method thereof |
| CN105012248A (en) * | 2014-04-29 | 2015-11-04 | 北京蓝丹医药科技有限公司 | Injection alprostadil fat emulsion and preparing method thereof |
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