CN101091791A - Injection of brain peptide, and preparation method - Google Patents
Injection of brain peptide, and preparation method Download PDFInfo
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- CN101091791A CN101091791A CN 200610086413 CN200610086413A CN101091791A CN 101091791 A CN101091791 A CN 101091791A CN 200610086413 CN200610086413 CN 200610086413 CN 200610086413 A CN200610086413 A CN 200610086413A CN 101091791 A CN101091791 A CN 101091791A
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Abstract
The present invention relates to a cerebropeptide injection and its preparation method. Said cerebropeptide injection contains hypermnesia peptide which can be dissolved in physiological saline, and its composition includes (by weight portion) 4-12 portions of hypermnesia peptide, 6000-13000 portions of sodium chloride and 500000-1500000 portions of water. It can be used for hypodermic injection, and can be used for raising memory and improving dysmnesia.
Description
Technical field
The present invention relates to a kind of injection of brain peptide and preparation method thereof, the memory-improving peptides injection and preparation method thereof of more specifically saying so.
Background technology
The research of the polypeptide of relevant influence memory and to be applied in field such as medical science of many uses, but relevant report is less.
Chinese invention patent 93112493.X (hypermnesia peptide and application thereof) discloses a kind of synthetic polypeptide that can promote the learning and memory function, i.e. hypermnesia peptide (MEP).Through the chemical simulation design, molecular dynamics is calculated and the active kinetic energy of binding synthetic peptide is measured, should can be made into various forms of medicines and beverage/food by synthetic peptide, be used for health care or treatment learning memory disorder, for example promote the brain early development, strengthen adult learning memory and treatment senile disease dementia etc.
Chinese invention patent 00116876.2 (memory-improving peptides and their purposes) continues the structure of synthetic polypeptide is transformed on the basis of above-mentioned patent, carries out pharmacological testing, improves the defective that existing polypeptide exists; This polypeptide can make by solid-phase polypeptide synthetic method or liquid phase polypeptide synthesis, and synthesis step is as follows:
Reaction is spent the night.
The same 1,2 handles.
The new hypermnesia peptide of this patent disclosure is simple in structure, production is convenient, pharmacological action is stronger, and can improve teenage children ' s intelligence development, adult's dysnoesia and amnesia, man memory function clinically and play facilitation.
Summary of the invention
The purpose of this invention is to provide a kind of injection of brain peptide.
Another object of the present invention provides the preparation method of above-mentioned injection of brain peptide.
Include the hypermnesia peptide of the effective dose that is dissolved in medicinal solvent in the injection of brain peptide of the present invention, the chemical structural formula of this hypermnesia peptide is:
Wherein,
Described X is Ala, Leu, Ile, Cys, Phe, Tyr or Val;
Described R
1Be PyroGlu or H;
Described R
2Be S-S-C (CH
3)
3Or S-C (CH
3)
3
In the injection of brain peptide of the present invention, the consumption of hypermnesia peptide is by Glacial acetic acid salt.Described injection of brain peptide, it can be mainly to be made by the raw material of following weight portion:
Hypermnesia peptide 4-12 part
Sodium chloride 6000-13000 part
Water 500000-1500000
Hypermnesia peptide is by Glacial acetic acid salt.
Described injection of brain peptide, it can be mainly to be made by the raw material of following weight portion:
8 parts of hypermnesia peptides
9000 parts in sodium chloride
1000000 parts in water
Hypermnesia peptide is by Glacial acetic acid salt.
The preparation method of injection of brain peptide of the present invention comprises the steps:
(1) takes by weighing sodium chloride, add entry, stir and make dissolving;
(2) get described hypermnesia peptide, add entry, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/LHCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Described injection of brain peptide, when it is mainly made by the raw material of following weight portion:
8 parts of hypermnesia peptides
9000 parts in sodium chloride
1000000 parts in water
Hypermnesia peptide is by Glacial acetic acid salt;
It can comprise the steps:
(1) takes by weighing 9000 parts in sodium chloride, add 800000 parts of entry, stir and make dissolving;
(2) get 8 parts of described hypermnesia peptides, add 200000 parts of entry, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/LHCl and 1mol/LnaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Above-mentioned injection of brain peptide need not adjuvant, but also can add nutrients such as aminoacid or saccharide, protein stabiliser and pH buffer etc., acid-base value maintains between the pH4.0-7.5.Generally do not need buffer, the acid-base value of brain peptide own maintains between the pH4.5-6.5.
The present invention is through evidence, the administration of brain peptide subcutaneous injection, and mice is kept away the memory acquisition disturbance that scopolamine hydrobromide causes in the dark experiment the improvement effect.The antagonism amnemonic effect that scopolamine caused is arranged in the mice water maze laboratory.
The specific embodiment
Embodiment 1
Get following raw material:
Hypermnesia peptide 4mg
Sodium chloride 6.5g
Water 1400ml
Hypermnesia peptide is by Glacial acetic acid salt.
Operation as follows:
(1) takes by weighing above-mentioned sodium chloride, add entry 1000ml, stir and make dissolving;
(2) get described hypermnesia peptide, add entry 400ml, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/LHCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Make 2800 altogether, every specification 0.0014mg/0.5ml/ props up
Embodiment 2
The weight portion of getting following each raw material is:
Hypermnesia peptide 8mg
Sodium chloride 9g
Water 1000ml
Hypermnesia peptide is by Glacial acetic acid salt.
Operation as follows:
(1) takes by weighing above-mentioned sodium chloride, add entry 800ml, stir and make dissolving;
(2) get described hypermnesia peptide, add entry 200ml, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/LHCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Make 2000 altogether, every specification 0.004mg/0.5ml/ props up
Embodiment 3
The weight portion of getting following each raw material is:
Hypermnesia peptide 11mg sodium chloride 12g water 600ml
Hypermnesia peptide is by Glacial acetic acid salt.
Operation as follows:
(1) takes by weighing above-mentioned sodium chloride, add entry 400ml, stir and make dissolving;
(2) get described hypermnesia peptide, add entry 200ml, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/LHCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Make 1200 altogether, every specification 0.0081mg/0.5ml/ props up
Embodiment 4
The animal efficiency assay that this example is carried out for Application Example 2 obtained products.
When rat skin lower injection and nasal spray, curve law was quite similar when the brain peptide fed the medicine of (0.1,0.5 and 2.0mg/Kg), and tail vein injection (0.5mg/Kg) drug-time curve meets the chamber rule of the easy molten class medicine of micromolecule.The performance of pharmacokinetic parameter medicine absorbs mutually fast, eliminates mutually slow rule, and the blood drug level of subcutaneous injection brain peptide increases with the increase of dosage.Dosage identical (0.5mg/kg) nasal spray and subcutaneous injection medicine similar A:164.08/172.36 on the intravital metabolic rule base of rat, ke:0.0070/0.0058, ka:2.748/2.240, T (peak): 2.177/2.665, C (max): 161.178/169.281, the subcutaneous injection blood drug level during than nasal spray exceeds 21.32%.
This research has been proved conclusively brain peptide aqueous solution by the nasal spray administration, medicine not only can be absorbed, and the speed, absorbtivity and the absorbing rule that absorb approach the result of subcutaneous injection administration, and the plasma drug level of 10min all is good linear relationship behind three kinds of dosages (0.1,0.5 and 2.0mg/Kg) medicine.The absolute bioavailability of subcutaneous administration is 75.8% when 0.5mg/kg.The absolute bioavailability of nasal spray administration is 78.7%.Show that these two kinds of administrations all have very high bioavailability, and their bioavailability basically identical.
Zoopery is effective:
Subcutaneous injection:
Drug efficacy study required the dysmnesia animal model according to new drug drug effect guideline before brain peptide subcutaneous injection was clinical, main observe the administration of medicine brain peptide to the influence of scopolamine hydrobromide induced mice learning memory disorder, observe the administration of brain peptide to scopolamine cause memory dysfunction influence, observe the administration of medicine brain peptide, the A β (25-35) of intracerebroventricular injection condensed state is caused the amnemonic influence of rat space learning.With administration scopolamine is caused that influence (water maze, the darkness avoidance test) result of memory dysfunction is as follows:
Darkness avoidance test: the time that normal mouse enters camera bellows is added up and respectively organized to experimental result is that incubation period and the number of times that pierces the darkroom are errors number.
The results are shown in following table 1
The effect (darkness avoidance test) of the memory acquisition disturbance that table 1 brain peptide causes scopolamine hydrobromide
| Group | Dosage | Incubation period (second) | Errors number (inferior) |
| Model group | ?99.5±104.35 | ?1.42±1 | |
| The normal control group | ?202.1±115.54 * | ?0.5±0.52 * | |
| Piracetam | 500mg/kg | ?191.25±92.13 * | ?0.75±0.62 * |
| The brain peptide | 2μg/kg | ?116.38±87.68 | ?1.38±0.65 |
| The brain peptide | 1μg/kg | ?227.75±97.05 ** | ?0.75±0.87 * |
| The brain peptide | 0.5μg/kg | ?196.5±83.47 * | ?1±0.6 |
N＝12
Compare with model group
*P＜0.05,
*P＜0.01
From last table result as can be seen each the group compare with model group, keep away in the dark experiment mice, the administration of brain peptide subcutaneous injection can prolong incubation period, and the errors number of going into cecum is also had significant difference.
Normal mouse, the water maze method the results are shown in following table 2,3
The effect (water maze) of the memory acquisition disturbance that table 2 brain peptide causes scopolamine hydrobromide
| Group | Dosage | Incubation period (second) | ||
| First day | Second day | The 3rd day | ||
| Model group | ?24.2±7.5 | ?91.1±28.4 | ?94.3±33.3 | |
| The normal control group | ?36±28 | ?80.8±33.2 | ?56.7±37.3 * | |
| The brain peptide | 2μg/kg | ?29.4±19.1 | ?74.1±30.2 | ?54.2±31.2 ** |
| The brain peptide | 1μg/kg | ?25.9±17.5 | ?81.7±32.3 | ?51.7±31.2 ** |
| The brain peptide | 0.5μg/kg | ?24.1±13 | ?55.2±31.5 * | ?49±37.1 ** |
N=12
*Compare P＜0.05 with model group,
*P＜0.01
The effect (water maze) of the memory acquisition disturbance that table 3 brain peptide causes scopolamine hydrobromide
| Group | Dosage | Errors number | ||
| First day | Second day | The 3rd day | ||
| Model group | 2.04±2.04 | ?5.71±2.39 | ?6.95±2.8 | |
| The normal control group | 2.29±2.19 | ?5.17±1.53 | ?4.46±2.88 * | |
| The brain peptide | 2μg/kg | 2.21±2.39 | ?5.88±2.42 | ?4.23±2.51 * |
| The brain peptide | 1μg/kg | 1.62±1.37 | ?6.88±2.32 | ?4.42±2.36 * |
| The brain peptide | 0.5μg/kg | 2.42±2.22 | ?5.12±2.76 | ?4.46±3.06 |
N＝12
*Compare P＜0.05 with model group
There were significant differences aspect incubation period in the 2nd day low dose of brain peptide group of training and scopolamine model group as can be seen from table 2,3.Compare with the scopolamine model group in each group of the 3rd day normal control group, the administration of brain peptide subcutaneous injection of training that all there were significant differences aspect incubation period and errors number.
Conclusion: the administration of brain peptide subcutaneous injection, mice is kept away the memory acquisition disturbance that scopolamine hydrobromide causes in the dark experiment the improvement effect.The antagonism amnemonic effect that scopolamine caused is arranged in the mice water maze laboratory.
Claims (5)
1, a kind of injection of brain peptide is characterized in that: this injection of brain peptide includes the hypermnesia peptide that is dissolved in normal saline, and its chemical structural formula is:
Wherein,
Described X is Ala, Leu, Ile, Cys, Phe, Tyr or Val;
Described R
1Be PyroGlu or H;
Described R
2Be S-S-C (CH
3)
3Or S-C (CH
3)
3
In the described injection of brain peptide, the consumption of hypermnesia peptide is by Glacial acetic acid salt.
2, injection of brain peptide according to claim 1 is characterized in that, described injection is made by the raw material of following weight portion:
Hypermnesia peptide 4-12 part
Sodium chloride 6000-13000 part
Water 500000-1500000.
3, injection of brain peptide according to claim 2 is characterized in that, described injection is made by the raw material of following weight portion:
8 parts of hypermnesia peptides
9000 parts in sodium chloride
1000000 parts in water.
4, the preparation method of the described injection of brain peptide of claim 1-3 is characterized in that, described method comprises the steps:
(1) takes by weighing sodium chloride, add entry, stir and make dissolving;
(2) get described hypermnesia peptide, add entry, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/L HCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
5, preparation method according to claim 4 is characterized in that, described method comprises the steps:
(1) takes by weighing 9000 parts in sodium chloride, add 800000 parts of entry, stir and make dissolving;
(2) get 8 parts of described hypermnesia peptides, add entry 200000, stir and make dissolving;
(3) gained solution in (2) is added gained solution in (1), stir;
(4) gained solution in (3) is regulated pH to 4.0-6.5 with 1mol/L HCl and 1mol/LNaOH solution;
(5) with 0.22 μ m filtering with microporous membrane, be sub-packed in the ampoule, every 0.5ml seals;
(6) 100 ℃ of circulation steam sterilizations 30 minutes, promptly.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610086413 CN101091791A (en) | 2006-06-19 | 2006-06-19 | Injection of brain peptide, and preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610086413 CN101091791A (en) | 2006-06-19 | 2006-06-19 | Injection of brain peptide, and preparation method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101091791A true CN101091791A (en) | 2007-12-26 |
Family
ID=38990349
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610086413 Pending CN101091791A (en) | 2006-06-19 | 2006-06-19 | Injection of brain peptide, and preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101091791A (en) |
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2006
- 2006-06-19 CN CN 200610086413 patent/CN101091791A/en active Pending
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