CN105203540A - Pancreatic leakage detection agent based on divalent cobalt ions and application of pancreatic leakage detection agent - Google Patents

Pancreatic leakage detection agent based on divalent cobalt ions and application of pancreatic leakage detection agent Download PDF

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Publication number
CN105203540A
CN105203540A CN201510594565.1A CN201510594565A CN105203540A CN 105203540 A CN105203540 A CN 105203540A CN 201510594565 A CN201510594565 A CN 201510594565A CN 105203540 A CN105203540 A CN 105203540A
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China
Prior art keywords
pancreas
detection agent
leaks
divalent cobalt
bivalent
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CN201510594565.1A
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Chinese (zh)
Inventor
刘祥瑞
周泉
李素静
苗毅
陆子鹏
蒋奎荣
唐建斌
申有青
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Zhejiang University ZJU
Jiangsu Province Hospital First Affiliated Hospital With Nanjing Medical University
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Zhejiang University ZJU
Jiangsu Province Hospital First Affiliated Hospital With Nanjing Medical University
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Priority to CN201510594565.1A priority Critical patent/CN105203540A/en
Publication of CN105203540A publication Critical patent/CN105203540A/en
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Abstract

The invention relates to the technical field of medical detection, in particular to a pancreatic leakage detection agent based on divalent cobalt ions and application of the pancreatic leakage detection agent. The pancreatic leakage detection agent is a solution containing divalent cobalt compound or is a water absorption material loaded with divalent cobalt compound, and is prepared by dissolving divalent cobalt compounds in solvent to prepare a solution or dropwise adding the divalent cobalt compounds to the water absorption material after the divalent cobalt compounds are dissolved in solvent. The divalent cobalt compounds are one of all cobalt-containing compounds which can generate divalent cobalt ions in solvent through ionization. By means of the pancreatic leakage detection agent, tissue liquid with pancreatic juice and tissue liquid without pancreatic juice can be distinguished through obvious color changes under the condition of low-dosage pancreatic juice, the high detection flexibility and the large detection range are achieved, and the pancreatic leakage detection agent is safe and reliable.

Description

A kind of pancreas based on divalent cobalt ion leaks detection agent and application thereof
Technical field
The present invention relates to medical detection technology, be specifically related to a kind of pancreas based on divalent cobalt ion and leak detection agent and application thereof.
Background technology
Pancreas fistula is complication the most common and serious after pancreatic surgery, is the one of the main reasons causing pancreatic surgery pneumoretroperitoneum severe infections and massive haemorrhage.The main cause of pancreas fistula is after operation stitching, the crack that some place is little because operation stitching exists, and occurs that pancreatic juice reveals (pancreas leakages), accumulates after pancreatic juice exosmoses in abdominal cavity, cause the pancreatin in pancreatic juice to be activated digestion.But pancreatic juice is a kind of liquid of colorless and odorless, so whether doctor exists pancreatic juice after the very first time cannot judging operation stitching accurately reveal, how to make pancreatic juice reveal the visual key just having become prevention pancreas fistula.
In pancreatic juice, magnesium hydrogen salt concentration is higher, and maximum concentration can reach 140mmol/L, and be tens times of surrounding tissue liquid, and concentration increases with the increase of pancreatic secretion speed, this makes the pH of pancreatic juice higher, reaches 7.8 ~ 8.5.Therefore, the different of the pH value of pancreatic juice and normal structure liquid can be utilized, pancreatic juice be revealed and diagnoses.
(YamaguchiKetal.Litmuspaperhelpsdetectpotentialpancreatoe nterostomyleakage [J] .AmJSurg such as YamaguchiK, 1998,175 (3): 227-8.) litmus paper being met alkali can introduce in art by the simple principle of red stain indigo plant, in order to test the position that on tangent plane, pancreatic juice overflows.The method adopted is, behind development location, the pancreatotropin of quiet note 50U is to stimulate the secretion of pancreatic juice, finds that pancreatic juice wipes dry tangent plane with dry gauze or filter paper after overflowing very soon, sticks the aseptic litmus paper through autoclaving process immediately.Originally, can see that red litmus paper reacts in diffuse blueness after contacting with pancreatic juice, after several times changing test paper, then can see blueness reaction test paper only presenting point-like, these Bluepoints fit tube opening little of cross-section pancreas, and the position of namely pancreatic juice leakage is corresponding.
Publication number be CN102247648A patent document discloses a kind of drainage tube testing leakage of digestive juice, along its pipe to posting acid test paper, litmus paper and cholerythrin test paper on this drainage tube inwall, the rubber drain outer wall that test paper is mapped separately is used corresponding words identification respectively.This drainage tube testing leakage of digestive juice is in drainage process, if there is the situation that pancreas leaks, color change will be there is in corresponding litmus paper, and the situation that words identification doctor energy Timeliness coverage intestines leak, pancreas leaks, stomach leaks and courage leaks by mapping, for Clinical Processing provides diagnosis and treatment timely and effectively.
Above-mentioned two parts of documents all meet alkali based on litmus paper then can by the simple principle of red stain indigo plant.But, the color range of litmus paper is 5.0 ~ 8.0, within the scope of physiological pH and pancreatic juice pH, color change is not clearly, simultaneously due to after pancreatic juice leaks, also can run into the neutralization of normal structure liquid, the pancreatic juice pH detected so actual is often lower than 8.0, now litmus paper is then more ineffective, simultaneously the dose requirements revealed pancreatic juice of reindeer moss is higher, sometimes pancreatic secretion must be stimulated by intravenous injection secretin, consider that pancreatic juice often less (20 μ l) is revealed in the short time clinically, this also greatly limit the use of litmus paper.And the security of litmus paper is unknown, may bring other spinoff to patient, really enters Clinical practice and need discussion.
Therefore, how under the condition of low dosage (20 μ l) pancreatic juice, obviously distinguishing pancreatic juice and tissue fluid, is the problem needing to solve.Meanwhile, the security ensureing testing process is wished.
Summary of the invention
The invention provides a kind of pancreas based on divalent cobalt ion and leak detection agent and application thereof, under the condition of low dosage pancreatic juice, the tissue fluid with or without pancreatic juice can be distinguished by obvious color change, there is higher detection sensitivity and larger sensing range, safe and reliable.
Pancreas provided by the invention leaks detection agent, comprises the absorbent material that solution containing bivalent Co or load have bivalent Co.
Described bivalent Co is all wherein one that can ionize out the cobalt compound of divalent cobalt ion in a solvent; As preferably, described bivalent Co is CoCl 2, CoSO 4, Co (NO 3) 2or Co (CH 3cOO) 2.These compounds are easy to get safely, and low price.
Described bivalent Co more preferably CoCl 2.CoCl 2make the desmacyte hyperplasia of normal person and Anemic patients, mean constant of red blood cell increases, and is used for the treatment of anaemia accordingly.
The solvent that solution containing bivalent Co adopts is water, C 2~ C 10alcohols or water and C 2~ C 10the potpourri of alcohols.
Described water and C 2~ C 10in the potpourri of alcohols, water and C 2~ C 10the volume ratio of alcohols is 1: (1 ~ 10).In this volume range, bivalent Co fully dissolves in a solvent.Consider that economy is easy to get, more preferably water or absolute ethyl alcohol.
The weight percent concentration of described bivalent Co solution is 0.1% ~ saturated.In this concentration range, it is higher that obtained pancreas leaks detection agent sensitivity, and low concentration (0.1%) bivalent Co can obtain good Detection results.As preferably, the weight percent concentration of described bivalent Co solution is 0.1% ~ 0.3%, and in this concentration range, to leak the security of detection agent higher for pancreas.
Described absorbent material is that filter paper, gauze etc. can the materials of absorbent solution; Consider that economy is easy to get and water absorbing properties is good, more preferably filter paper or gauze.
The charge capacity of bivalent Co on absorbent material is that the solution containing bivalent Co can by the minimum of absorbent material infiltration to saturated.Within the scope of this charge capacity, pancreas leaks detection agent obvious tissue fluid distinguished with or without pancreatic juice under the condition of low dosage (20 μ l) pancreatic juice, avoids intravenous injection secretin to stimulate pancreatic secretion, alleviates patient suffering.
The preparation method that described pancreas leaks detection agent is:
Bivalent Co is dissolved the solution obtained in a solvent containing bivalent Co, obtain pancreas and leak detection agent; Or bivalent Co is obtained in a solvent the solution containing bivalent Co, load is on absorbent material, dry, obtains the absorbent material that load has bivalent Co, obtains pancreas and leaks detection agent.
Wherein, the mode of load on absorbent material is: be added drop-wise on absorbent material by the solution containing bivalent Co, or immersed in the solution of bivalent Co by absorbent material.Dry mode comprises oven dry and natural air drying, is volatilized by solvent.
In order to understand the present invention better, principle of the present invention is mainly as follows:
Co 2++H 2O 2→Co 3++OH -+ ·OH
·OH+H 2O 2→HO 2 ·+H 2O
H ++HCO 3 --→H 2O+CO 2
2O 2 ·-+2O 2 ·-+4H 2O→(O 2) 2+2H 2O 2+4OH -
(O 2) 2 *→2O 2+hv(λ=490~500nm)
First divalent cobalt ion (Co 2+) catalysis H 2o 2decompose and first produce hydroxyl radical free radical (OH) and hydroperoxyl radical (HO 2), (HO 2) ionization generation peroxide root free radical (O 2 -) and H +, H +ion meets HCO 3 -or CO 3 2-, generate water and CO 2, CO 2for gas leaves solution, balance is moved right, (O 2 -) be polymerized again, produce the oxygen (O of high-energy singlet 2) 2, (O 2) 2strong chemiluminescence is produced when returning ground state.Under natural light condition, be viewed as in solution and have bubble to emerge, color becomes navy.
According to above-mentioned principle, the pancreas based on divalent cobalt ion leaks the application of detection agent in detection pancreas leaks and comprises:
1) when pancreas leakage detection agent is the solution containing bivalent Co:
By 1% ~ 3%H 2o 2aqueous solution and patient tissue liquid are added drop-wise to pancreas successively and leak in detection agent, leave standstill.Leak if pancreas occurs patient, this pancreas leaks detection agent will there is the change of obvious color, and has bubble to produce.
2) when pancreas leak detection agent be load have an absorbent material of bivalent Co time:
Before detection through 1% ~ 3%H 2o 2activated in water solution, pancreas after activation leaks on detection agent and drips patient tissue liquid, or the pancreas leakage detection agent after activation applies at patient wound's suture through sterilizing.Leak if pancreas occurs patient, this pancreas leaks detection agent will there is the change of obvious color.
As preferably, applying the concentration of leaking the bivalent Co that detection agent contains at the pancreas of patient wound's suture through sterilizing is 0.1% ~ 0.3%.Bivalent Co security in the concentration range of 0.1% ~ 0.3% is higher, reduces and leaks to pancreas the risk that patient causes secondary injury.
Described obvious color change does not comprise CoCl 2the pancreas prepared leaks detection agent and may occur becoming blue situation, because CoCl 2self being long placed in easily water suction in atmosphere and becoming blue, instead of pancreatic juice and this pancreas leak the result that detection agent reacts; CoCl 2the pancreas prepared leaks detection agent in use, leaks if pancreas occurs patient, and pancreas leaks detection agent will present yellow.
Beneficial effect of the present invention is mainly reflected in:
(1) pancreas of the present invention leaks the detectable pH scope of detection agent is 7.8 ~ 8.5, compared with litmus paper, pancreas leakage detection agent obviously can distinguish the tissue fluid with or without pancreatic juice within the scope of this pH, patient tissue liquid for pH≤8 is also suitable for, contribute to Timeliness coverage pancreatic juice leak site, maximum possible avoids the generation of pancreas fistula;
(2) pancreas leakage detection agent of the present invention sensitivity is higher, and low concentration (0.1%) bivalent Co can obtain good Detection results; This detection agent can distinguish the tissue fluid with or without pancreatic juice under the condition of low dosage (20 μ l) pancreatic juice, avoids intravenous injection secretin to stimulate pancreatic secretion, alleviates patient suffering;
(3) compared with litmus paper, it is higher that pancreas of the present invention leaks detection agent security, wherein CoCl 2with 1% ~ 3%H 2o 2aqueous solution clinically all useful and, within the scope of finite concentration, other potential safety hazards can't be brought to patient.
Accompanying drawing explanation
Fig. 1 is that the pancreas that embodiment 1 obtains leaks detection agent without H 2o 2during pre-service, detect variable concentrations HCO 3 -the result of solution.
Fig. 2 is that the pancreas that embodiment 1 obtains leaks detection agent through H 2o 2after pre-service, detect variable concentrations HCO 3 -the result of solution.
Fig. 3 is that the obtained pancreas of embodiment 1 leaks the color developing detection result of detection agent to pancreatic juice and serum.
Fig. 4 is that the obtained pancreas of embodiment 2 leaks detection agent with or without H 2o 2naHCO is detected under condition 3result.
Fig. 5 is the color developing detection result of comparative example 1 pair of pancreatic juice and serum.
Embodiment
Below in conjunction with embodiment, the invention will be further described.The present embodiment is implemented under premised on technical solution of the present invention, gives detailed embodiment and process, but protection scope of the present invention includes but not limited to following embodiment.
Embodiment 1:
Take 0.5gCoCl 2be dissolved in 100mlH 2in O, stir, ultrasonicly make it dissolve obtained CoCl 2solution; By this CoCl 2solution is added drop-wise on filter paper, dries, and pancreas obtained of the present invention leaks detection agent.
The HCO of configuration 10mmol/L, 50mmol/L, 100mmol/L and 150mmol/L 3-solution (solvent is water), leaks the Detection results of detection agent for detecting the obtained pancreas of embodiment 1:
A) according to Fig. 1 (in Fig. 1, "+" represents dropping), 50 μ lH are only dripped when pancreas leaks detection agent surface 2during O, not there is significant change, as a control group;
When pancreas leaks detection agent without 3%H 2o 2aqueous solution pre-service, only leaks at pancreas the HCO that detection agent surface drips 50 μ l50mmol/L 3 -solution, compared with control group, pancreas leaks detection agent and significant change does not occur; Similarly, at other without 3%H 2o 2the pretreated pancreas of aqueous solution leaks the HCO that detection agent surface drips 50 μ l100mmol/L and 150mmol/L respectively 3 -solution, compared with control group, pancreas leaks detection agent and significant change does not occur.
Show that the pancreas that embodiment 1 obtains leaks detection agent through 3%H 2o 2aqueous solution pre-service is steps necessary.The edge dripping solution in Fig. 1 may become blue or red, this is because CoCl 2self be long placed in easily water suction in atmosphere and become blue, CoCl 2solution itself is aobvious red, does not therefore leak as pancreatic juice and this pancreas the metachromatism that detection agent reacts.
B) according to Fig. 2 (in Fig. 2, "+" represents dropping), 50 μ l3%H are only dripped when pancreas leaks detection agent surface 2o 2during aqueous solution, not there is significant change, as a control group;
50 μ l3%H are dripped when pancreas leaks on detection agent 2o 2aqueous solution carries out pre-service, then drips 50 μ l10mmol/LHCO 3 -solution, compared with control group, pancreas leaks detection agent surface and slightly turns yellow; Similarly, at other through 50 μ l3%H 2o 2the pretreated pancreas of aqueous solution leaks the HCO that detection agent surface drips 50 μ l50mmol/L, 100mmol/L and 150mmol/L respectively 3 -solution, compared with control group, pancreas leaks detection agent and obviously turns yellow; Further, along with HCO 3 -the increase of solution concentration, pancreas leaks detection agent yellowing degree to be increased.
The above results shows, pancreas prepared by embodiment 1 leaks detection agent through H 2o 2after pre-service, HCO 3 -cause this pancreas to leak detection agent and remarkable metachromatism occurs, thus detect HCO 3 -existence.
The edge dripping solution in Fig. 2 may become blue or red, because CoCl 2self be long placed in easily water suction or oxidation in atmosphere, do not leak as pancreatic juice and this pancreas the metachromatism that detection agent reacts.
C) according to Fig. 3, leak patient from pancreas and obtain pancreatic juice, recording pH is 8.37; Replace normal structure liquid with the serum of tire ox, recording pH is 7.51.First use 1ml3%H 2o 2aqueous solution pre-service pancreas leakage detection agent, is added drop-wise to this pancreas and leaks on detection agent by pancreatic juice and each 1ml of serum, visible: it is white that this pancreas leaks detection agent chance serum color, its colour changed into yellow after chance pancreatic juice.
In order to both contrasts difference of color more significantly, have the right that the pancreas of serum leaks detection agent to drip 20 μ l pancreatic juice dripping, the region of visible white originally turns yellow instantaneously, and and periphery white portion have larger color distortion.
The above results shows, pancreas prepared by embodiment 1 leaks detection agent through H 2o 2after pre-service, the pancreatic juice of low dosage (20 μ l) namely causes this pancreas leakage detection agent that remarkable variable color occurs, and normal structure liquid then can not cause this pancreas to leak detection agent variable color, thus detects whether pancreas leakage occurs.
Embodiment 2:
Take 0.5gCoCl 2be dissolved in 100mlH 2in O, stir, ultrasonicly make it dissolve, obtain pancreas of the present invention and leak detection agent.
Utilize the obtained pancreas of embodiment 2 to leak detection agent to test as follows:
As shown in Figure 4,
The pancreas that embodiment 2 obtains leaks detection agent certainly as redness.
When only adding 20 μ l100mmol/LNaHCO 3during aqueous solution, the pancreas originally taken on a red color leaks detection agent color and becomes cinerous.
When being added with 20 μ l100mmol/LNaHCO simultaneously 3aqueous solution and 20 μ l3%H 2o 2during aqueous solution, the pancreas originally taken on a red color leaks detection agent color and becomes navy.
The above results shows, pancreas prepared by embodiment 2 leaks detection agent through H 2o 2after pre-service, HCO 3 -cause this pancreas to leak detection agent and remarkable variable color occurs, thus detect HCO 3 -existence.
Comparative example 1:
(1) extract random three patient's pancreatic juice, obtain three parts of different samples, record pH and be respectively 8.37,7.87 and 8.64;
(2) replace normal structure liquid with the serum of tire ox, pH is measured as 7.51;
(3) above-mentioned sample and each 20 μ l of serum are added drop-wise on litmus paper, observe color change.
As shown in Figure 5, the change of litmus paper color is not clearly, and (real pancreatic juice amount of leakage is little clinically when the amount of pancreatic juice is little, 20 μ about l), normal structure liquid and pancreatic juice can not make a distinction by litmus paper well, for clinical diagnosis brings inconvenience.

Claims (9)

1. the pancreas based on divalent cobalt ion leaks a detection agent, comprises the absorbent material that solution containing bivalent Co or load have bivalent Co.
2. the pancreas based on divalent cobalt ion according to claim 1 leaks detection agent, it is characterized in that: described bivalent Co is all wherein one that can ionize out the cobalt compound of divalent cobalt ion in a solvent.
3. the pancreas based on divalent cobalt ion according to claim 2 leaks detection agent, it is characterized in that: described bivalent Co is CoCl 2, CoSO 4, Co (NO 3) 2or Co (CH 3cOO) 2.
4. the pancreas based on divalent cobalt ion according to claim 1 leaks detection agent, it is characterized in that: the solvent that the described solution containing bivalent Co adopts is water, C 2~ C 10alcohols or water and C 2~ C 10the potpourri of alcohols.
5. the pancreas based on divalent cobalt ion according to claim 4 leaks detection agent, it is characterized in that: described water and C 2~ C 10in the potpourri of alcohols, water and C 2~ C 10the volume ratio of alcohols is 1: 1 ~ 10.
6. the pancreas based on divalent cobalt ion according to claim 1 leaks detection agent, it is characterized in that: the weight percent concentration of described bivalent Co solution is 0.1% ~ and saturated.
7. the pancreas based on divalent cobalt ion according to claim 1 leaks detection agent, it is characterized in that: described absorbent material is filter paper or gauze.
8. the pancreas based on divalent cobalt ion according to claim 1 leaks detection agent, it is characterized in that: the charge capacity of bivalent Co on absorbent material is that the solution containing bivalent Co can by the minimum of absorbent material infiltration to saturated.
9. the pancreas based on divalent cobalt ion according to claim 1 leaks the application of detection agent in detection pancreas leaks, and comprising:
When pancreas leakage detection agent is the solution containing bivalent Co:
By 1% ~ 3%H 2o 2aqueous solution and patient tissue liquid are added drop-wise to pancreas successively and leak in detection agent, leave standstill; Leak if pancreas occurs patient, this pancreas leaks detection agent will there is the change of obvious color, and has bubble to produce;
When pancreas leak detection agent be load have an absorbent material of bivalent Co time:
Before detection through 1% ~ 3%H 2o 2activated in water solution, pancreas after activation leaks on detection agent and drips patient tissue liquid, or the pancreas leakage detection agent after activation applies at patient wound's suture through sterilizing; Leak if pancreas occurs patient, this pancreas leaks detection agent will there is the change of obvious color.
CN201510594565.1A 2015-09-18 2015-09-18 Pancreatic leakage detection agent based on divalent cobalt ions and application of pancreatic leakage detection agent Pending CN105203540A (en)

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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2307573Y (en) * 1997-06-18 1999-02-17 刘广庆 Pancreiatic duct T-shape drainage tube
US20090192558A1 (en) * 2008-01-30 2009-07-30 Whitehurst Todd K Methods and systems of treating pancreatitis pain
CN102247648A (en) * 2011-04-11 2011-11-23 西安交通大学 Drainage tube capable of testing leakage of digestive juice
EP2857830A1 (en) * 2012-05-30 2015-04-08 The University of Tokyo Fluorescent probe for high-sensitivity pancreatic fluid detection, and method for detecting pancreatic fluid

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN2307573Y (en) * 1997-06-18 1999-02-17 刘广庆 Pancreiatic duct T-shape drainage tube
US20090192558A1 (en) * 2008-01-30 2009-07-30 Whitehurst Todd K Methods and systems of treating pancreatitis pain
CN102247648A (en) * 2011-04-11 2011-11-23 西安交通大学 Drainage tube capable of testing leakage of digestive juice
EP2857830A1 (en) * 2012-05-30 2015-04-08 The University of Tokyo Fluorescent probe for high-sensitivity pancreatic fluid detection, and method for detecting pancreatic fluid

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KOJI YAMAGUCHI.ET AL: "Litmus Paper Helps Detect Potential Pancreatoenterostomy Leakage", 《AMERICAN JOURNAL OF SURGERY》 *
SHU-XUAN LIANG.ET AL: "Experimental Studies on the Chemiluminescence Reaction Mechanism of Carbonate/ Bicarbonate and Hydrogen Peroxide in the Presence of Cobalt(II)", 《JOURNAL OF PHYSICAL CHEMISTRY A》 *

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Application publication date: 20151230