CN103893118A - Fat emulsion injection - Google Patents
Fat emulsion injection Download PDFInfo
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- CN103893118A CN103893118A CN201210580198.6A CN201210580198A CN103893118A CN 103893118 A CN103893118 A CN 103893118A CN 201210580198 A CN201210580198 A CN 201210580198A CN 103893118 A CN103893118 A CN 103893118A
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- injection
- lecithin
- oil
- nimodipine
- soybean
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Abstract
The invention includes a fat emulsion injection formulation and a preparation method, and the fat emulsion injection is prepared from the following main components by weight: 0.001-0.3% of nimodipine, 0.01-10% of lecithin and soybean lecithin, 10-30% of natural refined soybean oil for injection or other natural refined oil for injection, 0-10% of glycerol (glycerin) and the proper amount of water for injection by multiple times of high pressure homogenization.
Description
Technical field
The invention belongs to field of medicaments, relate to the calcium antagonist medicine nimodipine (Nimoldipine) of cerebrovascular smooth muscle, be particularly related to the calcium antagonist nimodipine Nimoldipine of cerebrovascular smooth muscle, Nimotop, Ni Lisu, precious according to quiet, extremely derivant fat milk injection and preparation method thereof of one or more in Ni Daer and their salt compound.
Background technology
Nimodipine (Nimoldipine) high selectivity acts on cerebrovascular smooth muscle, and expansible cerebrovascular also strengthens cerebral blood flow, improves cerebral blood supply level, has protective effect to removing cerebral vasospasm and cerebral infarction ischemic region tissue.Clinical research shows; this medicine scalable calcium ionic current enters neurocyte; first electrical properties and neurohumoral balance affect the nerves; the crowd many to cerebrovascular risk factor; nimodipine (Nimoldipine) as cerebral vessels protective agent to tide over distress phase; be usually used in prevention and the treatment of acute ischemic stroke, and improve prognosis.Nimodipine (Nimoldipine) is to act on stronger vasodilator, is used for the treatment of ischemic cerebrovascular, and the patient who merges brain cardiovascular disease is comparatively ideal medicine, and without obvious adverse reaction.
Nimodipine (Nimoldipine) is poorly water soluble drugs, and the liver first-pass effect that dissolubility is little and stronger, causes oral administration biaavailability low, and the bioavailability of health volunteer and Patients with Subarachnoid Hemorrhage is respectively 5%～13% and 3%～28%.This medicine biological half-life short (approximately 1.5～2h), often 3～4 frequent medications day by day, are not only used inconvenience, and can make blood drug level occur " peak valley " phenomenon, cause toxic and side effects; Commercially available nimotop vial has used a large amount of ethanol to make solvent, large to skin irritation, and patient is difficult to accept, and preparation stability is poor, easily occurs that medicine separates out.
Lipomul is a kind of dosage form with film affinity, permeability and carrier function, and medicine is written into lipomul and can reduces poisonous side effect of medicine, improve bioavailability and have long-acting slow-release effect.Nimodipine (Nimoldipine) fat milk injection not only can solve the solubility of medicine, reduces skin irritation, improves the preparation stability of this medicine, also can increase drug absorption, improves the bioavailability of nimodipine (Nimoldipine).
Summary of the invention
The present invention is to provide extremely preparation method of a kind of fat milk injection active component.
The active component that Nimodipine fat emulsion injection comprises has (1) nimodipine (Nimoldipine); (2) as soybean lecithin or Ovum Gallus domesticus Flavus lecithin and the derivant thereof of emulsifying agent, pharmaceutical carrier; (3) as natural refined soybean oil or other natural refined oil of injection of oil phase solvent; (4) as the glycerol (glycerol) of isoosmotic adjusting agent;
Nimodipine (Nimoldipine) consumption as principal agent composition is 0.001～0.3% (weight ratio);
Be 0.01～10% (weight ratio) as the soybean lecithin of emulsifying agent, pharmaceutical carrier or Ovum Gallus domesticus Flavus lecithin and derivant thereof containing the consumption of lecithin (PC);
The natural refined soybean oil of injection or the natural refined oil consumption of other injection as oil phase solvent are 10～30% (weight ratios);
Consumption as the glycerol (glycerol) of isoosmotic adjusting agent is 0～10% (weight ratio);
By the preparation of all or part of preparation fat milk injection of above-claimed cpd.
Nimodipine fat emulsion injection, is characterized in that, said as principal agent composition: nimodipine (Nimoldipine), and Nimotop, Ni Lisu, precious according to quiet, one or more in Ni Daer and their salt compound.
According to the Nimodipine fat emulsion injection of claim 1, it is characterized in that, the said soybean lecithin as emulsifying agent, pharmaceutical carrier or Ovum Gallus domesticus Flavus lecithin and derivant thereof can be: one or more in Ovum Gallus domesticus Flavus lecithin, soybean lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, synthetic lecithin, sphingomyelins.Wherein the purity of the said Ovum Gallus domesticus Flavus lecithin as emulsifying agent or soybean phospholipid and derivant thereof should be at 50-95% (Phosphotydylcholine, the content of PC) for Nimodipine fat emulsion injection.
Nimodipine fat emulsion injection, is characterized in that, saidly as oil phase solvent natural essential oil soybean oil can be: do one or more of any natural refined oil of injection.
The present invention has following advantage:
Nimodipine (Nimoldipine) is poorly water soluble drugs, and the liver first-pass effect that dissolubility is little and stronger, causes oral administration biaavailability low, and frequent medication is not only used inconvenience, and can make blood drug level occur " peak valley " phenomenon, causes toxic and side effects; Commercially available nimotop vial has used a large amount of ethanol to make solvent, large to skin irritation, and patient is difficult to accept, and preparation stability is poor, easily occurs that medicine separates out.
This is dissolved in the present invention fat-soluble medicine in natural refined oil, has avoided stimulation and the toxic and side effects of organic solvent to skin.
Buddhist nun is not poorly soluble in water, and commercially available Nimodipine Injeetion is placed and within one month, just had medicine to separate out at refrigerator, and the present invention can increase dissolubility, the raising preparation stability of medicine, and product is placed a year and a half at refrigerator and separated out there are no medicine.
Clinical data shows: lipomul can increase drug absorption, strengthens drug effect, extends action time.
Clinical data shows: lipomul has certain slow release effect, compared with oral formulations, can reduce dosage, and effect is lasting.
What the present invention disputed on without appearance possesses novelty, creativeness and practicality.
invention prescription, preparation technology, technological process
One, Nimodipine fat emulsion injection prescription and each component act in prescription
1. Nimodipine fat emulsion injection best prescription (1000ml)
| Title | Weight ratio (%) | Inventory |
| Nimodipine | 0.02 | 0.2 g |
| Refined soybean oil | 10 | 100g |
| Lecithin or soybean phospholipid | 1.2 | 12.0g |
| Glycerol | 2.25 | 22.5g |
| 2% sodium hydroxide | In right amount | In right amount |
| Water for injection | 88 | 880 ml |
2. the effect of each component in prescription
| Title | The effect of prescription |
| Nimodipine | Principal agent |
| Refined soybean oil | Solvent |
| Lecithin or soybean phospholipid | Emulsifying agent |
| Glycerol | Isoosmotic adjusting agent |
| 2% sodium hydroxide | PH regulator |
| Water for injection | Solvent |
Two, the preparation of Nimodipine fat emulsion injection
Whole fat milk production process is carried out under nitrogen protection.
Take lecithin or soybean phospholipid, refined soybean oil, heating for dissolving under electromagnetic agitation, cools.
Take nimodipine 0.22g, add in above-mentioned fluid, be stirred to dissolve 1..
Separately measure water for injection, glycerol, add appropriate 2% sodium hydroxide (NaOH), stir 2..
Will be 1. under agitation (450 revs/min) add 2., mix, through high pressure homogenizer homogenizing 7-8 time, pressure is 20～100MPa, mensuration pH value of solution 7.0～8.5.
With 0.8 micron of filtering with microporous membrane, fill nitrogen subpackage.
115 DEG C of flowing steam sterilizations 30 minutes.Obtain the fat milk drug solution of particle size range at 180-500nm, product should be uniform milky solution, not precipitation, lamination.
Product is preserved with warding off under optical condition at 2-15 DEG C.
product is prepared production example
The present invention verifies the amount ranges of listed main component.Under technology and condition of the present invention, the arbitrary consumption in nimodipine (Nimoldipine) consumption 0.001～0.3% scope can be made stable final products.
embodiment 1:the preparation of Nimodipine fat emulsion injection
1.1 Nimodipine fat emulsion injection prescriptions: make 1000 ml
| Title | Weight ratio (%) | Inventory |
| Nimodipine | In right amount | 0.1 g |
| Refined soybean oil | 10 | 100g |
| Soybean lecithin | 1.2 | 12.0g |
| Glycerol | 2.25 | 22.5g |
| 2% sodium hydroxide | In right amount | In right amount |
| Water for injection | 88 | 880 ml |
1.2 Nimodipine fat emulsion process for preparation of injection
Whole fat milk production process is carried out under nitrogen protection.
Take soybean lecithin, refined soybean oil, heating for dissolving under electromagnetic agitation, cools.
Take nimodipine, add in above-mentioned fluid, be stirred to dissolve 1..
Separately measure water for injection, glycerol, add appropriate 2% sodium hydroxide (NaOH), stir 2..
Will be 1. under agitation (450 revs/min) add 2., mix, through high pressure homogenizer homogenizing 7-8 time, pressure is 20～100MPa, mensuration pH value of solution 7.0～8.5.
With 0.8 micron of filtering with microporous membrane, fill nitrogen subpackage.
115 DEG C of flowing steam sterilizations 30 minutes.Obtain the fat milk drug solution of particle size range at 180-500nm, product should be uniform milky solution, not precipitation, lamination.
Product is preserved with warding off under optical condition at 2-15 DEG C.
embodiment 2:the preparation of Nimodipine fat emulsion injection
2.1 Nimodipine fat emulsion injection prescriptions: make 1000 ml
| Title | Weight ratio (%) | Inventory |
| Nimodipine | In right amount | 0.2g |
| Refined soybean oil | 10 | 100g |
| Ovum Gallus domesticus Flavus lecithin | 1.2 | 12.0g |
| Glycerol | 2.25 | 22.5g |
| 2% sodium hydroxide | In right amount | In right amount |
| Water for injection | 88 | 880 ml |
2.2 Nimodipine fat emulsion process for preparation of injection
Whole fat milk production process is carried out under nitrogen protection.
Take Ovum Gallus domesticus Flavus lecithin, refined soybean oil, heating for dissolving under electromagnetic agitation, cools.
Take nimodipine, add in above-mentioned fluid, be stirred to dissolve 1..
Separately measure water for injection, glycerol, add appropriate 2% sodium hydroxide (NaOH), stir 2..
Will be 1. under agitation (450 revs/min) add 2., mix, through high pressure homogenizer homogenizing 7-8 time, pressure is 20～100MPa, mensuration pH value of solution 7.0～8.5.
With 0.8 micron of filtering with microporous membrane, fill nitrogen subpackage.
115 DEG C of flowing steam sterilizations 30 minutes.Obtain the fat milk drug solution of particle size range at 180-500nm, product should be uniform milky solution, not precipitation, lamination.
Product is preserved with warding off under optical condition at 2-15 DEG C.
Claims (4)
1. a fat milk injection, is characterized in that: the active component comprising has:
1) nimodipine (Nimoldipine); 2) as soybean lecithin or Ovum Gallus domesticus Flavus lecithin and the derivant thereof of emulsifying agent, pharmaceutical carrier; 3) as natural refined soybean oil or the natural refined oil of other injection of oil phase solvent; 4) as the glycerol (glycerol) of isoosmotic adjusting agent;
Nimodipine (Nimoldipine) consumption as principal agent composition is 0.001～0.3% (weight ratio);
Be 0.01～10% (weight ratio) as the soybean lecithin of emulsifying agent, pharmaceutical carrier or Ovum Gallus domesticus Flavus lecithin and derivant consumption thereof;
The natural refined soybean oil of injection or the natural refined oil consumption of other injection as oil phase solvent are 10～30% (weight ratios);
Consumption as the glycerol (glycerol) of isoosmotic adjusting agent is 0～10% (weight ratio);
By all or part of preparation fat milk injection of above-claimed cpd.
2. a kind of fat milk injection according to claim 1, is characterized in that, said as principal agent composition: nimodipine (Nimoldipine), and Nimotop, Ni Lisu, precious according to quiet, one or more in Ni Daer and their salt compound.
3. a kind of fat milk injection according to claim 1, it is characterized in that, the said soybean lecithin as emulsifying agent, pharmaceutical carrier or Ovum Gallus domesticus Flavus lecithin and derivant thereof can be: extremely derivant of one or more in Ovum Gallus domesticus Flavus lecithin, soybean lecithin, hydrogenated yolk lecithin, hydrogenated soy phosphatidyl choline, synthetic lecithin, sphingomyelins.
4. a kind of fat milk injection according to claim 1, is characterized in that, saidly as oil phase solvent natural essential oil soybean oil can be: do one or more of any natural refined oil of injection.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210580198.6A CN103893118A (en) | 2012-12-28 | 2012-12-28 | Fat emulsion injection |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210580198.6A CN103893118A (en) | 2012-12-28 | 2012-12-28 | Fat emulsion injection |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103893118A true CN103893118A (en) | 2014-07-02 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201210580198.6A Pending CN103893118A (en) | 2012-12-28 | 2012-12-28 | Fat emulsion injection |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103893118A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688686A (en) * | 2015-02-10 | 2015-06-10 | 万全万特制药江苏有限公司 | Fat emulsion injection containing ziprasidone and salts thereof |
-
2012
- 2012-12-28 CN CN201210580198.6A patent/CN103893118A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104688686A (en) * | 2015-02-10 | 2015-06-10 | 万全万特制药江苏有限公司 | Fat emulsion injection containing ziprasidone and salts thereof |
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Application publication date: 20140702 |