CN108174843B - A kind of glucagon protective agent and its application - Google Patents
A kind of glucagon protective agent and its application Download PDFInfo
- Publication number
- CN108174843B CN108174843B CN201810066819.6A CN201810066819A CN108174843B CN 108174843 B CN108174843 B CN 108174843B CN 201810066819 A CN201810066819 A CN 201810066819A CN 108174843 B CN108174843 B CN 108174843B
- Authority
- CN
- China
- Prior art keywords
- glucagon
- protective agent
- sample
- blood
- protective
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Classifications
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N1/00—Preservation of bodies of humans or animals, or parts thereof
- A01N1/02—Preservation of living parts
- A01N1/0205—Chemical aspects
- A01N1/021—Preservation or perfusion media, liquids, solids or gases used in the preservation of cells, tissue, organs or bodily fluids
- A01N1/0226—Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
Abstract
The invention discloses a kind of glucagon protective agents, including 10~100g/L of anti-coagulants；2.5~150g/L of antioxidant；1~100g/L of serpin；0.1~5g/L of surfactant；0.02~4mmol/L of DPP-IV inhibitor；20~200mmol/L of buffer solution；0.1~10ml/L of biological preservative.The protective agent is mainly used for the protection of glucagon in blood sample, and self performance is stablized, while having obvious effect to the stability for improving glucagon.
Description
Technical field
The present invention relates to polypeptide preservation fields, and in particular to a kind of glucagon protective agent and its application.
Background technology
Glucagon, also referred to as glycemic element are a kind of hormones secreted by pancreas alpha Cell of islet, by 29 amino acid groups
At straight-chain polypeptide, molecular weight 3485.
Diabetes are one group of Metabolic Syndrome characterized by chronic blood glucose level increases, insulin and pancreas hyperglycemia
Element is critically important for maintaining blood glucose level appropriate.Insulin is exported by the intake of increase glucose periphery and reduction from liver
Glucose acts on liver and peripheral tissues to reduce blood glucose level, at the same time, glucagon by on liver cell
Glucagon receptor combines, and causes hepatic glycogenolytic and discharges the glucose stored in the form of glycogen, to help to maintain blood
Glucose level in liquid.As these storages are depleted, glucagon stimulation liver synthesizes additional Portugal by gluconeogenesis
Grape sugar, the glucose are discharged into blood flow, prevent the generation of hypoglycemia.
Glucagon clinically plays an important roll, and research, which has proven to glucagon, can promote liver cell inner ring
The biosynthesis of phosphorus adenosine (c-AMP), evaluates the liver reserve function of liver cirrhosis patient；Promote decomposition of glycogen and gluconeogenesis, rises
Hyperglycemia treats hypoglycemia；Inhibit gastrointestinal peristalsis, for cholangiopancreatography under gastrointestinal series and scope；Activate adenylate cyclisation
Enzyme enhances myocardial contractive power, treats intractable heart failure；Evaluate the clinical meanings such as diabetic's islet beta cell function.
In recent years, multiple drugmakers are dedicated to the development of glucagon analogue, and some is carrying out clinical test, having
Have been completed that clinical test enters market, show glucagon in the near future must become diabetes, angiocarpy
Etc. one of the common medicine of diseases.
Monitor glucagon changes of contents is for evaluation beta Cell of islet, glycemic control and related metabolic diseases
Treatment be essential premise.But glucagon is extremely unstable in blood sample, and very big shadow is brought to detection
It rings.How to keep stability of the glucagon in clinical sample, become glucagon quantify it is important in detection process
Factor.It has been reported that and adds Aprotinin in anticoagulated blood sample to protect the stability of glucagon, single Aprotinin molten
Liquid itself is unstable, inconvenient to use；The sample of added Aprotinin simultaneously, glucagon less stable therein, it is difficult to
Meets the needs of clinical detection.
Invention content
Present invention seek to address that problem as described above.The object of the present invention is to provide a kind of glucagon protective agent,
It is mainly used in the protection of glucagon in blood sample.The protective agent performance is stablized, while to improving glucagon
Stability has obvious effect.
According to an aspect of the present invention, the present invention provides a kind of glucagon protective agent, including following components, institutes
The content for stating each component is：
Wherein, including following components, the content of each component are：
Wherein, the antioxidant is one or more in curcumin, glutathione, l-methionine.
Wherein, the serpin is one or more in Aprotinin, trypsase.
Wherein, which is characterized in that the anti-coagulants is one or more in edetate, citrate；Institute
It is polysorbate fatty glyceride to state surfactant, one or more in fatty acid sorbitan；The DPP-IV inhibits
Agent is one or more in Xi Gelieting, vildagliptin, saxagliptin, Egelieting, Li Gelieting, teneligliptin；It is described
Buffer solution is Glycine-NaOH buffer solution；The biological preservative is one kind or more in ProClin300, KY-100
Kind.
Wherein, including following components, the content of each component are：
Wherein, including following components, the content of each component are：
Wherein, including following components, the content of each component are：
Wherein, the protectant dosage of the glucagon is the 1.5~2.5% of blood sample volume.
The glucagon protective agent provided according to another aspect of the present invention is steady in raising blood sample glucagon
Application on qualitative.
The present invention glucagon protective agent in anti-coagulants be edetate, one kind in citrate or
It is a variety of；Edetate can be disodium, dipotassium and tripotassium salt.Anti-coagulants can effectively chelate in blood preparation calcium from
Son prevents blood clotting；And edta salt can inhibit the activity of metalloproteinases, reduce metalloproteinases to glucagon
Hydrolysis.In protective agent of the present invention, the content of anti-coagulants is 10-100g/L；Preferably, it is 20~100g/L.
Antioxidant is one or more in curcumin, glutathione, l-methionine；Preferably, it is curcumin, paddy
The composition of the sweet peptide of Guang, l-methionine.Glucagon is by 29 amino acids formed straight-chain polypeptides, including first sulphur
The amino acid that propylhomoserin, arginine etc. are oxidized easily.These amino acid are more sensitive to oxygen radical, are oxidized easily, and can lead
It causes the structure of glucagon to change, and promotes the amyloid and fibrosis of glucagon, cause the poly- of glucagon
Collection.
Curcumin is a kind of acid polyphenols substance extracted from the rhizome of zingiberaceous plant turmeric etc., is turned into antioxygen
With.Research has shown that curcumin in vivo and in vitro, can directly remove the free radical in blood sample.Curcumin can pass through increase
Intracellular Glutathione is horizontal, to inhibit the generation of free radical, moreover, curcumin can also remove participation peroxidation
The free radical answered, anti-lipid peroxidation reaction, maintains the activity of various antioxidases.Curcumin can also promote amyloid egg
White decomposition, and prevent the formation of amyloid protein.
Glutathione is a kind of tripeptides synthesized naturally in human cell, is made of glutamic acid, cysteine and glycine.
Reduced glutathione therein can reduce the oxidation of oxidant, simultaneously by being combined with peroxide and free radical
Curcumin can be coordinated, inhibit the oxidation of free radical.
L-methionine is a kind of sulfur-containing amino acid, there is reproducibility.L-methionine can be to the first in glucagon
Methyllanthionine plays a protective role, and maintains the stabilization of glucagon structure.
By experimental verification, the antioxidant of 2.5-150g/L is added in protective agent, can keep blood sample well
The stabilization of middle glucagon structure；Preferably, antioxidant dosage is 30~130g/L.Still more preferably, it controls
Dosage：10~30g/L of curcumin；10~50g/L of l-methionine；10~50g/L of glutathione.
Glucagon is straight-chain polypeptide structure, and amino acid is exposed to outside, is very easy to be caused to tie by proteases for decomposing
The change of structure.In order to maintain the stabilization of glucagon structure, it is necessary to press down to the protease that structure may be caused to change
System makes these protease inactivate.So needs add the serpin and DPP- of certain content in protective agent
IV inhibitor.
Serpin is one or more in Aprotinin, trypsase；Preferably, it is Aprotinin.Suppression
Peptase is the single chain polypeptide extracted by ox lung, is broad-spectrum protease inhibitor, to various prokininases, trypsase, rotten albumen
Enzyme, fibrinolysin, pepsin etc. have inhibiting effect.Aprotinin forms reversible suppression by certain chemical ratios and repressed enzyme
Object-multienzyme complex processed inhibits and reduces the activity of enzyme.
DPP-IV is a kind of important serine hydrolase being distributed in the mammalian body, and it is living to participate in a variety of biologies in vivo
The hydrolysis of property polypeptide (such as glucagon, incretin, neuropeptide, gastrin releasing peptide, growth hormone releasing hormone)
And then it is caused partially or completely to inactivate.DPP-IV inhibitor can specificity inhibition DPP-IV enzymatic activity, it is right to reduce its
The decomposition of glucagon.In the present invention, DPP-IV inhibitor Xi Gelieting, vildagliptin, saxagliptin, A Gelie
Spit of fland, Li Gelieting, teneligliptin it is one or more.
The content of serpin be 1~100g/L, preferred 1~50g/L, still more preferably 1~
20g/L.The additive amount of DPP-IV inhibitor is 0.02~4mmol/L, preferred 0.02~2mmol/L.It is found through experiments that, adds
It is subject to the serpin and DPP-IV inhibitor of content, the two synergistic effect can inhibit pancreas height well
The degradation and aggregation of blood glucose element.
Surfactant is polysorbate (tween) fatty glyceride, one kind or more in fatty acid sorbitan (sapn)
Kind；Preferably, Tween-80 is added.The Tween-80 of 0.1~5g/L of addition can increase the dissolving of glucagon and curcumin
Property；Preferably, 0.1~3g/L is added.
The protective agent of the present invention uses Glycine-NaOH buffer solution.Glycine-NaOH buffer solution can be with
Stable alkaline environment is maintained, so that the lucid asparagus amino pepsin in blood is inactivated, prevents glucagon from degrading, glycine
There is certain inhibiting effect to the oxidation of glucagon.The content of buffer solution is advisable with 20~200mmol/L, it is preferred that 60
~200mmol/L.
Biological preservative is one or more in ProClin300, KY-100；Biological preservative is lived with broad-spectrum antiseptic
Property, can inhibit the growth of the microorganisms such as bacterium, fungi within the long time, at the same can in holding system enzyme activity.
Additive amount is in 0.1~10ml/L, preferably 0.1~3ml/L.
The glucagon protective agent of the present invention is applied on improving blood sample glucagon stability, and dosage is blood
The 1.5~2.5% of liquid sample volume are far below the additive amount of general liquid additive 5~10%.Its advantage is reduced to sample
The change of volume reduces the influence to testing result；In addition cost can be reduced, per the protective agent expense of mL blood sample additions
Only at 0.2~0.5 yuan or so.
Compared with the prior art, the protectant advantageous effect of glucagon of the invention is mainly reflected in：
1, the present invention has obvious effect to the stability for improving glucagon in blood sample.
2, specimen preservatives performance of the invention is stablized, and convenient for storage and uses.
3, composition of the present invention is simple, and material is cheap, is easy to get；Preparation process is simple, is suitble to industrialized production.
Specific implementation mode
In order to make the object, technical scheme and advantages of the embodiment of the invention clearer, below in conjunction with the embodiment of the present invention,
Technical scheme of the present invention is clearly and completely described, it is clear that described embodiment is that a part of the invention is implemented
Example, instead of all the embodiments.Based on the embodiments of the present invention, those of ordinary skill in the art are not making creativeness
The every other embodiment obtained under the premise of labour, shall fall within the protection scope of the present invention.It should be noted that not conflicting
In the case of, the features in the embodiments and the embodiments of the present application mutually can be combined arbitrarily.
The present invention provides a kind of glucagon protective agent, including following components, the content of each component are：Anti-coagulants 10~
100g/L；2.5~150g/L of antioxidant；1~100g/L of serpin；0.1~5g/L of surfactant；
0.02~4mmol/L of DPP-IV inhibitor；20~200mmol/L of buffer solution；0.1~10ml/L of biological preservative.
Preferably, the content of each component is：20~100g/L of anti-coagulants；30~130g/L of antioxidant；Serine stretch protein
1~50g/L of enzyme inhibitor；0.1~3g/L of surfactant；0.02~2mmol/L of DPP-IV inhibitor；Buffer solution 60~
200mmol/L；0.1~3ml/L of biological preservative.
Wherein, anti-coagulants is one or more in edetate, citrate；Antioxidant be curcumin,
It is one or more in glutathione, l-methionine；Serpin is one kind in Aprotinin, trypsase
Or it is a variety of；Surfactant is polysorbate fatty glyceride, one or more in fatty acid sorbitan；DPP-IV inhibits
Agent is one or more in Xi Gelieting, vildagliptin, saxagliptin, Egelieting, Li Gelieting, teneligliptin；Biology
Preservative is one or more in ProClin300, KY-100.
Specifically, the content of each component is：20~100g/L of edetate；10~30g/L of curcumin；L- first sulphur
10~50g/L of propylhomoserin；10~50g/L of glutathione；1~20g/L of Aprotinin；0.1~3g/L of surfactant；DPP-IV inhibits
0.02~2mmol/L of agent；60~200mmol/L of Glycine-NaOH buffer solution；0.1~3ml/L of ProClin300.
Embodiment
Protective agent preparation process：
1, the Glycine-NaOH buffer solution of a concentration of 20~200mmol/L of 100mL is prepared；
2, weigh respectively the curcumin of respective predetermined content, EDTAP dipotassium ethylene diamine tetraacetate, l-methionine, glutathione,
Tween-80, and it is dissolved in Glycine-NaOH buffer solution successively；0.01~1ml ProClin300 are measured, are dissolved in above-mentioned molten
Liquid；Mixing, filtering, 2~8 DEG C of placement are spare.
3, the above-mentioned solution of 10ml is taken, the Aprotinin of predetermined content, mixing dissolving are accurately weighed；Measure 2~400 μ l, concentration
For the DPP-IV inhibitor (teneligliptin) of 0.1mmol/mL, above-mentioned solution, mixing, 2~8 DEG C of preservations are added.
Above-mentioned material is commercially available product；Wherein, Aprotinin is purchased from Shanghai Aladdin biochemical technology limited liability company, turmeric
Element is purchased from Sigma companies, and DPP-IV inhibitor (teneligliptin) is purchased from MedChemexpress companies.
Table 1 shows the specific formula composition of some embodiments.It should be pointed out that protectant material of the present invention is matched
Side is not limited to data in table 1.
1 glucagon protective agent embodiment of table
Test case
The protectant preservation effect testing result of embodiment 1-7 glucagons is given below.
1, instrument, reagent and sample
Key instrument：Enzyme micro-plate reader, model RT-6000, Rayto Life and Analytical Sciences Co., Ltd.'s production.
Main agents：Glucagon detection kit (article No. 10-1271-01) is produced by Mercodia companies of Sweden.
Disposable human vein blood specimen collection container (EDTA2K), given birth to by the medical development in science and technology Co., Ltd of three power of Liuyang City
Production.
Glucagon protective agent：Embodiment 1-7 glucagon protective agents.
Sample：Blood sample derives from machin, is provided by south China Primate Research Center.
2, experimental program：
Machin fasting 12 hours or more uses disposable human vein blood specimen collection container to take a blood sample.Same machin is adopted
Blood 7 is managed, often pipe 2mL.The glucagon protective agent of 40 μ L embodiments 1-7, mixing is added after blood sampling immediately, centrifugation takes supernatant
Blood plasma, packing, glucagon stability at 2~8 DEG C of detection.
2 embodiment 1-7 testing result (units of table：pmol/L)
From table 2 it can be seen that sample, at 2~8 DEG C, with the growth of time, the glucagon detection in sample is tied
Fruit does not have significant change, illustrates the glucagon protective agent of the present invention to the protective effect of glucagon in sample very
By force.Wherein, embodiment 3, embodiment 6 and 7 protective effect of embodiment are most strong.
Comparative example
Comparative example 1
1, instrument, reagent and sample
Key instrument：Enzyme micro-plate reader, model RT-6000, Rayto Life and Analytical Sciences Co., Ltd.'s production.
Main agents：Glucagon detection kit (article No. 10-1271-01) is produced by Mercodia companies of Sweden.
Disposable human vein blood specimen collection container (EDTA2K), given birth to by the medical development in science and technology Co., Ltd of three power of Liuyang City
Production.
Glucagon protective agent is provided by Guangzhou into moral bio tech ltd.
Sample：Blood sample derives from machin, is provided by south China Primate Research Center.
2, experimental program：
Machin fasting 12 hours or more uses disposable human vein blood specimen collection container to take a blood sample.Machin is numbered
1-6, every machin blood sampling 5 are managed, often pipe 2mL.0.9% sodium chloride solution, 40 μ L (control groups are added after wherein the 1st blood sampling tube
1) 40 μ L (control group 2) of Aprotinin solution, are added after the 2nd blood sampling tube immediately, pancreas hyperglycemia is separately added into after the 3rd to 5 blood sampling tube
40 μ L of plain protective agent (experimental group, respectively embodiment 3, embodiment 6 and embodiment 7), after mixing, centrifugation takes supernatant blood plasma, point
Dress is used for detection.
Sample is detected by following preservation condition：
(1) it is detected immediately after centrifuging,
(2) 37 DEG C place 4 hours after detect,
(3) 2~8 DEG C place 24 hours after detect
(4) 6 sample of embodiment detects after placing 24,48,72,96 and 120 hours at 2~8 DEG C.
Pattern detection is executed according to glucagon detection kit (article No. 10-1271-01) specification.
3, experimental result：
Table 3 is the preservation situation detected immediately after control group 1, control group 2 and experimental group sample centrifuge, unit：pmol/
L。
3 pattern detection result of table
From table 3 it can be seen that the detected value of control group 1 is significantly lower than control group 2 and experimental group；Show that blood sample is handled
In the process, Aprotinin is not added, glucagon, which has, in sample largely degrades.
Control group 2 and the detected value of experimental group relatively, show that adding Aprotinin and the glucagon of the present invention protects
It is suitable to glucagon protective effect in blood sample to protect agent.
Table 4 is 37 DEG C of control group 1, control group 2 and experimental group sample preservation situations for placing 4 hours, unit：pmol/
L。
4 pattern detection result of table
From table 4, it can be seen that after sample is placed 4 hours at 37 DEG C, the testing result of control group 1 reduces clearly, connects
Nearly detection lower bound.The testing result of control group 2, which also has, significantly to be declined, and experimental group testing result decline degree is smaller, explanation
The glucagon protective agent of the present invention will be significantly greater than the protective effect of glucagon in sample and add under the conditions of 37 DEG C
Add Aprotinin group.
Table 5 is the preservation situation after 2~8 DEG C of control group 1, control group 2 and experimental group sample are placed 24 hours, unit：
pmol/L。
5 pattern detection result of table
As can be seen from Table 5, after sample is placed 24 hours at 2~8 DEG C, the testing result of control group 1 reduces clearly,
The testing result of control group 2, which also has, significantly to be declined, and experimental group testing result does not have significant change, illustrates that the pancreas of the present invention is high
Blood glucose element protective agent will be significantly greater than addition Aprotinin under the conditions of 2~8 DEG C, to the protective effect of glucagon in sample
Group.
6 protective agent of Example is as the protection feelings after 2~8 DEG C of experimental group observation placement 24,48,72,96 and 120 hours
Condition, unit：pmol/L.
6 pattern detection result of table
As can be seen from Table 6, sample is placed 120 hours at 2~8 DEG C, and the glucagon testing result in sample does not have
Significant change illustrates the glucagon protective agent of the present invention under the conditions of 2~8 DEG C, the protection to glucagon in sample
Effect is very strong, more meets the needs of clinical sample detection.
Comparative example 2
1, instrument, reagent and sample
Key instrument：Enzyme micro-plate reader, model RT-6000, Rayto Life and Analytical Sciences Co., Ltd.'s production.
Main agents：Glucagon detection kit (article No. 10-1271-01) is produced by Mercodia companies of Sweden.
Disposable human vein blood specimen collection container (EDTA2K), given birth to by the medical development in science and technology Co., Ltd of three power of Liuyang City
Production.
Glucagon protective agent：It is provided into moral bio tech ltd by Guangzhou.
Samples sources：Healthy volunteer.
2, experimental program：
Healthy volunteer, male, 10 people.It 12 hours or more on an empty stomach, is adopted using disposable human vein blood specimen collection container
Blood.Number 1-10, everyone 3 pipes of taking a blood sample, often pipe 2mL.0.9% sodium chloride solution, 40 μ L (control groups are added after wherein the 1st blood sampling tube
1) 40 μ L (control group 2) of Aprotinin solution, are added after the 2nd blood sampling tube immediately, glucagon protection is separately added into after the 3rd blood sampling
40 μ L of agent (experimental group, embodiment 6), after mixing, centrifugation takes supernatant blood plasma, dispenses, and is used for detection.
Sample is detected by following preservation condition：
(1) it is detected immediately after centrifuging,
(2) 37 DEG C place 4 hours after detect,
(3) 2~8 DEG C place 24 hours after detect
(4) 6 sample of embodiment detects after placing 24,48,72,96 and 120 hours at 2~8 DEG C.
Pattern detection is executed according to glucagon detection kit (article No. 10-1271-01) specification.
3, experimental result：
Table 7 is the preservation situation detected immediately after control group 1, control group 2 and experimental group sample centrifuge, unit：pmol/
L。
7 pattern detection result of table
As can be seen from Table 7, the detected value of control group 1 is significantly lower than control group 2 and experimental group, shows clinical blood sample
In processing procedure, Aprotinin is not added, glucagon, which has, in sample largely degrades.
Control group 2 and the detected value of experimental group relatively, show that adding Aprotinin and the glucagon of the present invention protects
It is suitable to the protective effect of glucagon in blood sample to protect agent.
Table 8 is 37 DEG C of control group 1, control group 2 and experimental group sample preservation situations for placing 4 hours, unit：pmol/
L。
8 pattern detection result of table
As can be seen from Table 8, after sample is placed 4 hours at 37 DEG C, the testing result of control group 1 reduces clearly, connects
Nearly detection lower bound.The testing result of control group 2, which also has, significantly to be declined, and experimental group testing result decline degree is smaller, explanation
The glucagon protective agent of the present invention will be significantly greater than the protective effect of glucagon in sample and add under the conditions of 37 DEG C
Add Aprotinin group.
Table 9 is the preservation situation after 2~8 DEG C of control group 1, control group 2 and experimental group sample are placed 24 hours, unit：
pmol/L。
9 pattern detection result of table
As can be seen from Table 9, after sample is placed 24 hours at 2~8 DEG C, the testing result of control group 1 reduces clearly,
The testing result of control group 2 also has a degree of decline, experimental group testing result then without significant change, to illustrate the present invention's
Glucagon protective agent will be significantly greater than addition suppression peptide under the conditions of 2~8 DEG C, to the protective effect of glucagon in sample
The control group 2 of enzyme.
Pancreas hyperglycemia after taking experimental group (embodiment 6) sample, 2~8 DEG C of observation to place 24,48,72,96 and 120 hours
Plain stable type, unit：pmol/L.
10 pattern detection result of table
As can be seen from Table 10, sample is placed 120 hours at 2~8 DEG C, the glucagon testing result in clinical sample
There is no significant change, illustrates the glucagon protective agent of the present invention under the conditions of 2~8 DEG C, to pancreas hyperglycemia in clinical sample
The protective effect of element is very strong, more meets the needs of clinical sample detection.
In conclusion glucagon protective agent performance provided by the invention is stablized, convenient for storage and use；To improving pancreas
The stability of glucagons has obvious effect；And protective agent preparation process is simple, and composition is simple, and material is easy to get, and price is just
Preferably.
Descriptions above can combine implementation individually or in various ways, and these variants all exist
Within protection scope of the present invention.
Finally it should be noted that：The above embodiments are merely illustrative of the technical solutions of the present invention, rather than its limitations.Although
Present invention has been described in detail with reference to the aforementioned embodiments, it will be understood by those of ordinary skill in the art that：It still may be used
With technical scheme described in the above embodiments is modified or equivalent replacement of some of the technical features；
And these modifications or replacements, various embodiments of the present invention technical solution that it does not separate the essence of the corresponding technical solution spirit and
Range.
Claims (9)
1. a kind of glucagon protective agent, which is characterized in that including following components, the content of each component is：
2. glucagon protective agent as described in claim 1, which is characterized in that including following components, each component
Content is：
3. glucagon protective agent as claimed in claim 1 or 2, which is characterized in that the antioxidant is curcumin, paddy
It is one or more in the sweet peptide of Guang, l-methionine.
4. glucagon protective agent as claimed in claim 3, which is characterized in that
The anti-coagulants is one or more in edetate, citrate；
The surfactant is polysorbate fatty glyceride, one or more in fatty acid sorbitan；
The DPP-IV inhibitor is in Xi Gelieting, vildagliptin, saxagliptin, Egelieting, Li Gelieting, teneligliptin
It is one or more；
The buffer solution is Glycine-NaOH buffer solution；
The biological preservative is one or more in ProClin300, KY-100.
5. glucagon protective agent as claimed in claim 4, which is characterized in that including following components, each component
Content is：
6. glucagon protective agent as claimed in claim 5, which is characterized in that including following components, each component
Content is：
7. glucagon protective agent as claimed in claim 5, which is characterized in that including following components, each component
Content is：
8. such as claim 1-7 any one of them glucagon protective agents, which is characterized in that the glucagon protection
The dosage of agent is the 1.5~2.5% of blood sample volume.
9. a kind of as steady in raising blood sample glucagon such as claim 1-7 any one of them glucagon protective agents
Application on qualitative.
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810066819.6A CN108174843B (en) | 2018-01-24 | 2018-01-24 | A kind of glucagon protective agent and its application |
| PCT/CN2018/117401 WO2019144692A1 (en) | 2018-01-24 | 2018-11-26 | Glucagon protectant and use thereof |
| JP2020538994A JP7158063B2 (en) | 2018-01-24 | 2018-11-26 | Glucagon protective agent and its application |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810066819.6A CN108174843B (en) | 2018-01-24 | 2018-01-24 | A kind of glucagon protective agent and its application |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN108174843A CN108174843A (en) | 2018-06-19 |
| CN108174843B true CN108174843B (en) | 2018-11-13 |
Family
ID=62551261
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810066819.6A Active CN108174843B (en) | 2018-01-24 | 2018-01-24 | A kind of glucagon protective agent and its application |
Country Status (3)
| Country | Link |
|---|---|
| JP (1) | JP7158063B2 (en) |
| CN (1) | CN108174843B (en) |
| WO (1) | WO2019144692A1 (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108174843B (en) * | 2018-01-24 | 2018-11-13 | 广州市进德生物科技有限公司 | A kind of glucagon protective agent and its application |
| CN110433169A (en) * | 2019-08-13 | 2019-11-12 | 复旦大学附属华山医院 | Adenosine is preparing the application in hypoglycemic drug |
| CN115039760A (en) * | 2022-06-16 | 2022-09-13 | 郑州安图生物工程股份有限公司 | Buffer matrix liquid and application thereof |
Family Cites Families (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NO893088L (en) * | 1988-08-18 | 1990-02-19 | Syntex Inc | PROCEDURE FOR THE PREPARATION OF THERAPEUTICALLY EFFECTIVE SOMATOSTAT SIMILAR CYCLE PEPTID RELATIONS. |
| US5541116A (en) * | 1991-09-30 | 1996-07-30 | B.R.A.H.M.S. Diagnostica Gmbh | Method for the stabilization of endogenous, physiologically active peptides |
| BR0309976A (en) * | 2002-05-13 | 2005-03-01 | Becton Dickinson Co | Protease Inhibitor Sample Collection System |
| CN101394848A (en) * | 2006-01-06 | 2009-03-25 | 诺瓦提斯公司 | Use of vildagliptin for the treatment of diabetes |
| CN101368172A (en) * | 2008-10-06 | 2009-02-18 | 上海理工大学 | Freeze drying protective agent for rubricyte and use method in freeze drying process |
| CN102144630B (en) * | 2011-02-12 | 2013-10-09 | 上海市血液中心 | Adding liquid for storing platelets under liquid low temperature condition and application thereof |
| JP5844826B2 (en) * | 2011-03-04 | 2016-01-20 | ベクトン・ディキンソン・アンド・カンパニーＢｅｃｔｏｎ， Ｄｉｃｋｉｎｓｏｎ Ａｎｄ Ｃｏｍｐａｎｙ | Blood collection device containing lysophospholipase inhibitor |
| EP2758533B1 (en) | 2011-09-20 | 2018-04-11 | Ionis Pharmaceuticals, Inc. | Antisense modulation of gcgr expression |
| CN203169191U (en) * | 2012-10-18 | 2013-09-04 | 付士明 | Vacuum blood collection tube for diabetes active peptide blood sample detection |
| US9334316B2 (en) | 2014-04-11 | 2016-05-10 | Oregon Health & Science University | Formulations comprising glucagon |
| US20160024559A1 (en) | 2014-07-24 | 2016-01-28 | The Bode Technology Group, Inc. | Specimen collection with reagent lined collectors |
| CN104931317B (en) * | 2015-06-11 | 2018-05-25 | 宁波美晶医疗技术有限公司 | A kind of blood pretreatment liquid |
| CA2995392C (en) | 2015-09-04 | 2023-08-15 | Hailiang Chen | Stabilized glucagon solutions |
| WO2017211917A1 (en) | 2016-06-07 | 2017-12-14 | Adocia | Compositions in the form of an injectable aqueous solution, comprising human glucagon and a statistical copolyamino acid |
| CN106872338A (en) * | 2017-02-28 | 2017-06-20 | 珠海丽珠圣美医疗诊断技术有限公司 | A kind of blood cell stabilizer and its application |
| CN108174843B (en) * | 2018-01-24 | 2018-11-13 | 广州市进德生物科技有限公司 | A kind of glucagon protective agent and its application |
-
2018
- 2018-01-24 CN CN201810066819.6A patent/CN108174843B/en active Active
- 2018-11-26 WO PCT/CN2018/117401 patent/WO2019144692A1/en active Application Filing
- 2018-11-26 JP JP2020538994A patent/JP7158063B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN108174843A (en) | 2018-06-19 |
| JP2021510205A (en) | 2021-04-15 |
| WO2019144692A1 (en) | 2019-08-01 |
| JP7158063B2 (en) | 2022-10-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN108174843B (en) | A kind of glucagon protective agent and its application | |
| CN109400678B (en) | Stichopus japonicus-derived antioxidant and DPP-IV inhibitory active peptide | |
| Yazdi et al. | Skeletal muscle mitochondrial depletion and dysfunction in chronic kidney disease | |
| Hoshino et al. | Oxidative post-translational modifications develop LONP1 dysfunction in pressure overload heart failure | |
| CZ20031900A3 (en) | Mixture of microbial enzymes | |
| Magrì et al. | Anemia and iron deficiency in heart failure: clinical and prognostic role | |
| CN107561257A (en) | A kind of detection method for assessing heparin class curative effect of medication and residual condition | |
| Olusegun et al. | Alpha-Amylase–inhibitory properties and in-vitro antioxidant potentials of cowpea seed protein hydrolysates | |
| CN1049865A (en) | Pure urokinase proenzyme and human serum albumin are by the plasminogen activators mixture of the covalently bound formation of disulfide bridge bond | |
| Jarmołowska et al. | Serum activity of dipeptidyl peptidase IV (DPPIV; EC 3.4. 14.5) in breast-fed infants with symptoms of allergy | |
| CN109932512A (en) | A kind of fibrinogen detection reagent/freeze-drying detection reagent and preparation method thereof completely inhibiting platelet function | |
| CN110812469B (en) | Application of polypeptide AR12 in preparation of antioxidant | |
| Zhou et al. | Protective effect of citrulline on the hearts of rats with sepsis induced by cecal ligation and puncture | |
| CN106473027A (en) | A kind of preparation method of tilapia fishskin liquid fermentation activated product | |
| Asakura et al. | Enzymatic reduction of spin-labeled ferrihemoglobin | |
| Simell | Diamino acid transport into granulocytes and liver slices of patients with lysinuric protein intolerance | |
| Hellsten et al. | Effects on fibrinolytic activity of corn oil and a fish oil preparation enriched with omega-3-polyunsaturated fatty acids in a long-term study | |
| CN103145800B (en) | Centipede zymolyte anti-thrombus polypeptide | |
| Alireza et al. | Effects of vitamin E on pathological changes induced by diabetes in rat lungs | |
| Prins et al. | The flux of arginine after ischemia-reperfusion in the rat kidney | |
| CN113087773B (en) | Yak bone peptide with blood sugar reducing and antioxidant functions and preparation method thereof | |
| Yao et al. | Novel chemiluminescence method for detection of superoxide anions and its application to dry-cured meat | |
| McNulty et al. | Nitrite consumption in ischemic rat heart catalyzed by distinct blood-borne and tissue factors | |
| JP7036324B2 (en) | Anti-blood coagulation agent, blood coagulation improving device, blood coagulation improving method, vascular endothelial cell function improving method and metabolism improving method | |
| Zheng et al. | Inhibition of NOS2 ameliorates cardiac remodeling, improves heart function after myocardial infarction in rats |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| PE01 | Entry into force of the registration of the contract for pledge of patent right |
Denomination of invention: A glucagon protective agent and its application Effective date of registration: 20200921 Granted publication date: 20181113 Pledgee: China Co. truction Bank Corp Guangzhou Liwan branch Pledgor: GUANGZHOU JINDE BIOTECHNOLOGY Co.,Ltd. Registration number: Y2020440000292 |
|
| PE01 | Entry into force of the registration of the contract for pledge of patent right | ||
| PC01 | Cancellation of the registration of the contract for pledge of patent right |
Date of cancellation: 20211013 Granted publication date: 20181113 Pledgee: China Co. truction Bank Corp Guangzhou Liwan branch Pledgor: GUANGZHOU JINDE BIOTECHNOLOGY Co.,Ltd. Registration number: Y2020440000292 |
|
| PC01 | Cancellation of the registration of the contract for pledge of patent right |