CN108392623A - A kind of agonist drug composition of steroid non-depolarizing muscular relaxant - Google Patents
A kind of agonist drug composition of steroid non-depolarizing muscular relaxant Download PDFInfo
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- CN108392623A CN108392623A CN201810074234.9A CN201810074234A CN108392623A CN 108392623 A CN108392623 A CN 108392623A CN 201810074234 A CN201810074234 A CN 201810074234A CN 108392623 A CN108392623 A CN 108392623A
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/08—Peptides having 5 to 11 amino acids
- A61K38/085—Angiotensins
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- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
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- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/08—Drugs for disorders of the alimentary tract or the digestive system for nausea, cinetosis or vertigo; Antiemetics
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P21/00—Drugs for disorders of the muscular or neuromuscular system
- A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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Abstract
This case discloses a kind of agonist drug composition of steroid non-depolarizing muscular relaxant, and the composition includes 6 deoxidation alpha amino acid derivative cyclodextrin, Metoclopramide, angiotensin II, anhydrous sodium acetate, sodium hydrogensulfite and citric acid.The 6 deoxidation alpha amino acid derivative cyclodextrin is the main component of the pharmaceutical composition；Metoclopramide is a kind of antiemetic, is subject to anhydrous sodium acetate, sodium hydrogensulfite assists, collective effect dopamine receptor in oblongata chemoreceptor trigger zone, to improve chemoreceptor trigger zone threshold value；Angiotensin II is one of Vasoconstrictor, whole body arteriole can be made to shrink, arterial pressure increases；It can effectively solve the agonist drug of existing steroid muscle relaxant as one of auxiliary material, occur decreased heart rate when in use, the ill symptoms that blood pressure declines.The drug collective effect provides a kind of effective agonist drug composition for reducing the steroid non-depolarizing muscular relaxants of ill symptoms such as vomiting, blood pressure reduction.
Description
Technical field
The present invention relates to medicinal chemistry arts, and in particular to a kind of agonist drug combination of steroid non-depolarizing muscular relaxant
Object.
Background technology
Muscle relaxant is also known as skeletal muscle relaxant or N2 cholinoreceptor blockers, can act selectively upon kinesitherapy nerve end
N2 receptors on plate film, block nerves are got excited to be transmitted to skeletal muscle, leads to muscle, skeletal muscle relaxation.But its without calm, anesthesia and
Analgesic activity.And when general anesthesia, it is not easy to endotracheal intubation, therefore, muscle relaxant changes after being used for clinical anesthesia by deepening general anesthesia
Obtain the requirement of flaccid muscles for meeting operation.Currently, muscle relaxant has become adjuvant drug important when general anesthesia, rapid induction is carried out
It is of flaccid muscles in endotracheal intubation and operation.In addition, muscle relaxant can be used for ventilated patients.
Muscle relaxant has different action time by the difference of injection volume.After operation at one, often muscle relaxant is also
It is acting on, to solve the technical problem, is inventing the antagonistic of muscle relaxant.And according to the difference of muscle relaxant type, needle is invented
To the antagonistic of the muscle relaxant of different role mechanism.Steroid muscle relaxant be middle effect non-depolarizing muscular relaxant, by with acetylcholine
Receptor Competition is combined and is acted.Such drug has Vecuronium Bromide and rocuronium etc..The medicine of the antagonistic of this kind of muscle relaxant
While reason is acetylcholine esterase inhibition, the N2 receptors on also directly exciting muscle cell membrane promote nerve endings to discharge acetyl
Choline.
The agonist drug of existing steroid muscle relaxant may occur in which that Nausea and vomiting, decreased heart rate, blood pressure decline when in use
Equal ill symptoms.It when ill symptoms are more serious, are often used mixed hyoscyamine and treated, but it can be to the short of money of steroid muscle relaxant
The drug effect of antiradiation drug is inhibited.
Invention content
In view of the above shortcomings of the prior art, it is an object of the present invention to provide a kind of steroid non-depolarizing muscular relaxants
Agonist drug composition effectively reduces the ill symptoms of the agonist drug of existing steroid muscle relaxant.
For achieving the above object, the technical scheme is that：
Wherein, 6- deoxidations alpha-amino acid derivatives cyclodextrin is the antagonistic of steroid muscle relaxants, is the agonist drug
The main component of composition, Metoclopramide are a kind of antiemetics, are subject to anhydrous sodium acetate, sodium hydrogensulfite for auxiliary material, jointly
It acts on dopamine receptor in oblongata chemoreceptor trigger zone and improves the threshold value of chemoreceptor trigger zone, there is powerful maincenter
Property anti-vomiting effect.Meanwhile also promoting the movement of stomach and top intestinal segment；The tension of quiescent condition gastrointestinal tract sphincter is improved, is increased
Add the tension of lower esophageal sphincter and the amplitude of contraction, lower esophagus pressure is made to increase, block gastroesophageal reflux, reinforces stomach and food
Pipe is wriggled, and is enhanced and cleaned up ability to esophageal contents, and the emptying of stomach is promoted, and promotes pylorus, duodenum and top jejunum
Relaxation, form the orthofunction that stomach body of stomach and top are oozed between intestines.Spit effect in the town that these effects also can enhance this product.These are made
Effect is spat with can also enhance town.The angiotensin II is most important component part in blood vessel progress element, is that contracting blood vessel is lived
Property one of substance, whole body arteriole can be made to shrink, arterial pressure increases；It can effectively solve existing steroid as one of auxiliary material
The agonist drug of muscle relaxant may occur in which the ill symptoms that decreased heart rate, blood pressure decline when in use.
As a preferred embodiment of the present invention, the agonist drug composition of the steroid non-depolarizing muscular relaxant, including
Following component：
As a preferred embodiment of the present invention, the agonist drug composition of the steroid non-depolarizing muscular relaxant, including
Following component：
As a preferred embodiment of the present invention, the 6- deoxidations alpha-amino acid derivatives cyclodextrin is 6- deoxidation sulfoxide groups
Alpha-amino acid derivatives cyclodextrin or 6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin.
As a preferred embodiment of the present invention, the pH of described pharmaceutical composition is 3-5.
As a preferred embodiment of the present invention, described pharmaceutical composition is liquid injection agent.Pass through intramuscular administration so that
Gastrointestinal smooth muscle promotes stomach to shrink and increases gastric acid secretion, and promotes small, large intestine, especially the wriggling of colon, to prevent
Enteron aisle relaxation promotes intestinal contents to advance downwardly.
As a preferred embodiment of the present invention, the solvent of the liquid injection agent is aqueous solvent.6- deoxidation alpha-amidos
Acid derivative cyclodextrin and Metoclopramide are water soluble compound.Therefore, fluid present invention injection solvent is selected as water-soluble
Property solvent.
Further include PEARLITOL 25C in the liquid injection agent as a preferred embodiment of the present invention.
As a preferred embodiment of the present invention, the pH of the liquid injection agent is 7.2-7.4, and injection should have and blood
Liquid phase etc. or similar pH value.The normal value of the pH of blood is generally in 7.35-7.45, and all intracellular biochemical changes are by blood
The influence of liquid pH.When blood pH is less than 6.9 or higher than 7.7, life danger will occur.The injection of the present invention strictly controls
Between 7.2-7.4.
As a preferred embodiment of the present invention, the medicine-feeding part of the liquid injection agent is subcutaneous administrations.
The invention has the beneficial effects that：
The Metoclopramide with antiemetic effect is added in the antagonistic of the steroid muscle relaxant of the present invention, and not to 6- deoxidations α-
Amino acid derivativges cyclodextrin generates antagonism, greatly reduces the Nausea and vomiting of the antagonistic of existing steroid muscle relaxant
Ill symptoms.
The angiotensin II with boosting is added in the antagonistic of the steroid muscle relaxant of the present invention, and not to 6- deoxidations
Alpha-amino acid derivatives cyclodextrin generate antagonism, greatly reduce the antagonistic of existing steroid muscle relaxant decreased heart rate,
The ill symptoms that blood pressure declines.
Specific implementation mode
With reference to embodiment, the present invention is described in further detail, to enable those skilled in the art with reference to specification
Word can be implemented according to this.
One, pharmaceutical composition
Embodiment 1
6- deoxidation sulfoxide group alpha-amino acid derivatives cyclodextrin：0.25mg；
Metoclopramide：7mg；
Angiotensin II：0.2ng；
Anhydrous sodium acetate：1mg；
Sodium hydrogensulfite：0.8mg；
Citric acid：0.35mg；
pH：3.3；
Dosage form：Tablet.
Embodiment 2
6- deoxidation sulfoxide group alpha-amino acid derivatives cyclodextrin：0.3mg；
Metoclopramide：5mg；
Angiotensin II：0.1ng；
Anhydrous sodium acetate：1.1mg；
Sodium hydrogensulfite：0.7mg；
Citric acid：0.3mg；
pH：3.0；
Dosage form：Capsule.
Embodiment 3
6- deoxidation sulfoxide group alpha-amino acid derivatives cyclodextrin：0.4mg；
Metoclopramide：9mg；
Angiotensin II：0.1ng；
Anhydrous sodium acetate：1.5mg；
Sodium hydrogensulfite：1.1mg；
Citric acid：0.4mg；
pH：4.1；
Dosage form：Powder.
Embodiment 4
6- deoxidation sulfoxide group alpha-amino acid derivatives cyclodextrin：0.5mg；
Metoclopramide：11mg；
Angiotensin II：0.3ng；
Anhydrous sodium acetate：2mg；
Sodium hydrogensulfite：1.4mg；
Citric acid：0.37mg；
pH：3.7.
Dosage form：Powder.
Embodiment 5
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：0.8mg；
Metoclopramide：13mg；
Angiotensin II：0.4ng；
Anhydrous sodium acetate：2mg；
Sodium hydrogensulfite：1.6mg；
Citric acid：0.4mg；
pH：4.2.
Dosage form：Powder.
Embodiment 6
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：0.9mg；
Metoclopramide：18mg；
Angiotensin II：0.3ng；
Anhydrous sodium acetate：3mg；
Sodium hydrogensulfite：1.7mg；
Citric acid：0.5mg；
pH：5.0.
Dosage form：Liquid injection agent.
Embodiment 7
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：0.5mg；
Metoclopramide：11mg；
Angiotensin II：0.3ng；
Anhydrous sodium acetate：2mg；
Sodium hydrogensulfite：1.3mg；
Citric acid：0.4mg；
pH：3.9；
Dosage form：Liquid injection agent.
Embodiment 8
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：1mg；
Metoclopramide：20mg；
Angiotensin II：0.5ng；
Anhydrous sodium acetate：3mg；
Sodium hydrogensulfite：2.5mg；
Citric acid：0.5mg；
pH：5.0；
Dosage form：Liquid injection agent.
Two, liquid injection agent
Embodiment 9
6- deoxidation sulfoxide group alpha-amino acid derivatives cyclodextrin：0.3mg；
Metoclopramide：5mg；
Angiotensin II：0.1ng；
Anhydrous sodium acetate：1.1mg；
Sodium hydrogensulfite：0.7mg；
Citric acid：0.3mg；
Mannitol：0.1mg；
pH：7.2
Embodiment 10
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：0.9mg；
Metoclopramide：18mg；
Angiotensin II：0.3ng；
Anhydrous sodium acetate：3mg；
Sodium hydrogensulfite：1.7mg；
Citric acid：0.5mg；
PEARLITOL 25C：0.2mg；
pH：7.4.
Embodiment 11
6- deoxidation sulfuryl alpha-amino acid derivatives cyclodextrin：0.5mg；
Metoclopramide：11mg；
Angiotensin II：0.3ng；
Anhydrous sodium acetate：2mg；
Sodium hydrogensulfite：1.3mg；
Citric acid：0.4mg；
PEARLITOL 25C：0.2mg；
pH：7.3.
Clinical data
Embodiment 12
30 patients are selected, are divided into 15 groups, one group is control group, uses the antagonistic of existing steroid non-depolarizing muscular relaxant；
Another set is experimental group, uses the antagonistic of steroid non-depolarizing muscular relaxant in embodiment 7.Table one is what two groups of patients occurred
Differential responses.
Table one
| Group | Vomiting | Blood pressure declines |
| Control group | 3 | 5 |
| Experimental group | 0 | 0 |
Experiment shows that drug of the invention has effects that good antiemetic, prevents blood pressure from declining.And it is non-in antagonism steroid
It is close with existing antagonistic effect in terms of depolarizing relaxant effect.
Although the embodiments of the present invention have been disclosed as above, but its is not only in the description and the implementation listed
With it can be fully applied to various fields suitable for the present invention, for those skilled in the art, can be easily
Realize other modification, therefore without departing from the general concept defined in the claims and the equivalent scope, the present invention is simultaneously unlimited
In specific details.
Claims (10)
1. a kind of agonist drug composition of steroid non-depolarizing muscular relaxant, which is characterized in that including following component：
2. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 1, it is characterised in that：Including such as
Lower component：
3. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 1, it is characterised in that：Including such as
Lower component：
4. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 1, it is characterised in that：The 6-
Deoxidation alpha-amino acid derivatives cyclodextrin is 6- deoxidations sulfoxide group alpha-amino acid derivatives cyclodextrin or 6- deoxidation sulfuryl alpha-amidos
Acid derivative cyclodextrin.
5. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 1, it is characterised in that：The medicine
The pH of compositions is 3-5.
6. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 1, it is characterised in that：The medicine
The dosage form of compositions is liquid injection agent.
7. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 6, it is characterised in that：The liquid
The solvent of body injection is aqueous solvent.
8. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 6, it is characterised in that：The liquid
It further include PEARLITOL 25C in body injection.
9. the agonist drug composition of steroid non-depolarizing muscular relaxant according to claim 6, it is characterised in that：The liquid
The pH of body injection is 7.2-7.4.
10. the agonist drug composition of the steroid non-depolarizing muscular relaxant according to claim 6 to 9 any one, special
Sign is：The medicine-feeding part of the liquid injection agent is administered intramuscular.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810074234.9A CN108392623A (en) | 2018-01-25 | 2018-01-25 | A kind of agonist drug composition of steroid non-depolarizing muscular relaxant |
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| CN201810074234.9A CN108392623A (en) | 2018-01-25 | 2018-01-25 | A kind of agonist drug composition of steroid non-depolarizing muscular relaxant |
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591402A (en) * | 2009-05-05 | 2009-12-02 | 杭州奥默医药技术有限公司 | 6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof |
| CN102060941A (en) * | 2010-11-26 | 2011-05-18 | 漆又毛 | 6-deoxy alpha-amino acid derivative cyclodextrin, preparation and application thereof |
| CN105342997A (en) * | 2015-11-28 | 2016-02-24 | 山东齐都药业有限公司 | Metoclopramide hydrochloride injection and preparation method thereof |
-
2018
- 2018-01-25 CN CN201810074234.9A patent/CN108392623A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101591402A (en) * | 2009-05-05 | 2009-12-02 | 杭州奥默医药技术有限公司 | 6-deoxy-sulfones cyclodextrin derivatives and preparation method thereof |
| CN102060941A (en) * | 2010-11-26 | 2011-05-18 | 漆又毛 | 6-deoxy alpha-amino acid derivative cyclodextrin, preparation and application thereof |
| CN105342997A (en) * | 2015-11-28 | 2016-02-24 | 山东齐都药业有限公司 | Metoclopramide hydrochloride injection and preparation method thereof |
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