CN108310008B - Application of colloidal gold in preparation of artificial cerebrospinal fluid reagent - Google Patents
Application of colloidal gold in preparation of artificial cerebrospinal fluid reagent Download PDFInfo
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- CN108310008B CN108310008B CN201810020569.2A CN201810020569A CN108310008B CN 108310008 B CN108310008 B CN 108310008B CN 201810020569 A CN201810020569 A CN 201810020569A CN 108310008 B CN108310008 B CN 108310008B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
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- A—HUMAN NECESSITIES
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- A61K33/42—Phosphorus; Compounds thereof
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Abstract
The invention provides a new application of colloidal gold in the preparation of artificial cerebrospinal fluid, wherein the colloidal gold consists of colloidal gold particles with the particle size range of 5-25 mu m, the average particle size of 13.4 +/-3.6 mu m, the concentration of the colloidal gold of 150-400mg/L and the average particle size of 232.4 +/-38.3 mg/L. The invention can simulate the colloid osmotic pressure and the cell environment of the cerebrospinal fluid of a human body, and creates a novel artificial cerebrospinal fluid which is more in line with physiological characteristics.
Description
Technical Field
The invention belongs to the field of preparation of medical artificial cerebrospinal fluid, and particularly relates to application of colloidal gold in preparation of artificial cerebrospinal fluid.
Background
Cerebrospinal Fluid (CSF) is a colorless and transparent liquid that fills the ventricles of the brain, the subarachnoid space, and the central Spinal canal. Cerebrospinal fluid is produced by the choroid plexus in the ventricles and eventually permeates through the arachnoid granules in the subarachnoid space on the dorsal side of the brain into the superior sagittal sinus and flows back into the vein. Cerebrospinal fluid is similar to plasma and lymph fluid in nature, slightly viscous, and belongs toExtracellular fluid. Normal cerebrospinal fluid has a certain osmotic pressure, mainly consists of the osmotic pressure of crystals and the osmotic pressure of colloids, and plays an important role in maintaining the relative stability of cranial pressure. The total amount of cerebrospinal fluid of normal adult is about 150ml, its specific gravity is 1.003-1.008, protein content is 150-400mg/L, sugar content is 450-750mg/L, pH is 7.31-7.34, cell content is about 5X 106L, mainly lymphocytes and monocytes.
At present, the artificial cerebrospinal fluid gradually replaces the normal saline to carry out ventricular lavage, and the inorganic salt components (sodium, potassium, chlorine, calcium, magnesium, bicarbonate and phosphate) of the artificial cerebrospinal fluid replace the normal saline to replace, so that the flushing effect can be achieved, and the secondary damage to the damaged brain tissue can be avoided. The ion concentration, the pH value and the crystal osmotic pressure of the artificial cerebrospinal fluid are similar to those of human cerebrospinal fluid, so the artificial cerebrospinal fluid is safer in clinical application and is widely applied to ventricular lavage of subarachnoid hemorrhage, infectious meningitis, cerebral trauma and other diseases.
However, the artificial cerebrospinal fluid used clinically at present does not contain cellular components, the colloid osmotic pressure of the artificial cerebrospinal fluid is far away from the actual cerebrospinal fluid, and the application of the artificial cerebrospinal fluid can destroy the circulating homeostasis of the cerebrospinal fluid and cause the secondary edema and degeneration of nerve cells.
Disclosure of Invention
The invention provides a brand-new artificial cerebrospinal fluid. The colloidal components with controllable particle size and content are provided, the content of cells in cerebrospinal fluid is simulated, the colloid osmotic pressure caused by the circulation of the cerebrospinal fluid is maintained, and the colloidal components have important clinical significance.
The purpose of the invention is realized by the following measures:
application of colloidal gold in preparing artificial cerebrospinal fluid is provided.
The particle size of the colloidal gold is 5 to 25 μm. Preferably, the average particle size is 13.4. + -. 3.6. mu.m.
The invention also provides a colloidal gold preparation, wherein the concentration of the colloidal gold in the preparation is 150-400 mg/L; preferably at a concentration of 232.4. + -. 38.3 mg/L.
The colloidal gold preparation also comprises 6-7g/L of sodium chloride, 0.2-0.3g/L of potassium chloride, 0.3-0.4g/L of calcium chloride, 1.5-2.5g/L of sodium bicarbonate, 0.2-0.6g/L of magnesium chloride, 0.5-0.8g/L of glucose, 0.3-0.5g/L of disodium hydrogen phosphate and double distilled water as a solvent.
The colloidal gold preparation has good simulation effect on various cell structures, biomacromolecule structures, contents and the like of human cerebrospinal fluid, and has good simulation performance on the colloid osmotic pressure, ion osmotic pressure, pH value and the like of human cerebrospinal fluid.
The preparation method of the colloidal gold preparation adopts the reaction of chloroauric acid and trisodium citrate, the mass concentration of the chloroauric acid is 1 percent, and the concentration of the trisodium citrate is 0.0025 percent. In order to ensure that the grain diameter of the colloidal gold is in a proper range, the reaction temperature is 95 ℃, and the reaction time is 15 min.
Specifically, the method comprises the following steps: dissolving chloroauric acid crystals in distilled water at 25 ℃ to prepare a chloroauric acid solution with the concentration of 0.01%, heating to 95 ℃, and maintaining for 15 minutes; rapidly adding 250 μ l/L0.1% trisodium citrate water solution, heating while stirring for 30 min at a stirring speed of 200 rpm to obtain colloidal gold solution; filtering, centrifuging at 8000 rpm and 4 deg.C, and dissolving in water; adding sodium chloride, potassium chloride, calcium chloride, sodium bicarbonate, magnesium chloride, glucose and disodium hydrogen phosphate, and mixing.
In the operation, the required equipment is disinfected, the required raw materials are subjected to aseptic treatment, and the artificial cerebrospinal fluid containing the colloidal gold is scientifically prepared, so that the electrolyte and the pH value of the artificial cerebrospinal fluid are normal and strictly sterilized.
Advantageous effects
1. The invention utilizes the colloidal gold particles with the particle size and concentration similar to those of cells in the cerebrospinal fluid to complete the simulation of the artificial cerebrospinal fluid, solves the problem that the traditional artificial cerebrospinal fluid cannot simulate the osmotic pressure similar to that of the cerebrospinal fluid of a human body, simulates the cell environment in the cerebrospinal fluid, and creates a novel artificial cerebrospinal fluid which is more in line with the physiological characteristics.
2. The invention provides
The novel artificial cerebrospinal fluid has similar properties of osmotic pressure, pH value, specific gravity and the like with the cerebrospinal fluid of a human body.
3. Animal experiments prove that: the novel artificial cerebrospinal fluid flushing therapy can effectively reduce the hematoma amount after subarachnoid hemorrhage and simultaneously improve the occurrence of cerebral edema without obvious side effect.
4. The invention has simple raw materials, convenient and quick operation, stable structure and easy storage, and the colloidal gold particles can circulate along with cerebrospinal fluid.
Drawings
FIG. 1 Artificial cerebrospinal fluid containing colloidal gold particles prepared in example 1 was imaged under a microscope.
FIG. 2 gross hematoma on basis of skull in rats of the flushing group and the control group 7 days after subarachnoid hemorrhage in example 2.
FIG. 3 brain Water content of rats in the flushing group and the control group 7 days after subarachnoid hemorrhage in example 3.
Detailed Description
The present invention is further illustrated by the following specific examples.
Example 1
A method for preparing an artificial cerebrospinal fluid preparation containing colloidal gold comprises the following steps: dissolving chloroauric acid crystals in distilled water at 25 deg.C to obtain 100ml chloroauric acid solution with concentration of 0.01%, heating to 95 deg.C, and maintaining for 15 min; respectively and rapidly adding 25 μ l of 0.1% trisodium citrate aqueous solution, stirring for 30 min while heating, wherein the stirring speed is set to 200 r/min, and obtaining colloidal gold solution; filtering, centrifuging the colloidal gold solution at 8000 rpm and 4 deg.C, removing supernatant, dissolving with 100ml distilled water, centrifuging at 8000 rpm and 4 deg.C, and repeating for three times. 0.6279g of sodium chloride, 0.0216g of potassium chloride, 0.0353g of calcium chloride, 0.1932g of sodium bicarbonate, 0.0488g of magnesium chloride, 0.06g of glucose and 0.0358g of disodium hydrogen phosphate are added. Finally, the volume is adjusted to 100ml by double distilled water.
Introducing prepared artificial cerebrospinal fluid containing 95% of O2、5％CO2The mixed gas is saturated, and the pH value is adjusted to 7.31-7.34. The particle size of the artificial cerebrospinal fluid is 5-25 μm when the artificial cerebrospinal fluid is dispersed in the colloidal gold particles under microscope observation (figure 1). The osmotic pressure of the prepared artificial cerebrospinal fluid is measured to be 293.7mOsm/kg, and the specific gravity is 1.005. Is normalThe pH value of the cerebrospinal fluid of a human body is 7.31-7.34, the osmotic pressure is 280-310mOsm/kg, and the specific gravity is 1.003-1.008.
Example 2
Male Sprague-Dawley rats (with the weight of 250-: artificial cerebrospinal fluid containing colloidal gold was slowly pumped into the lateral ventricle (rate 0.5ml/h) and drained in the lumbar cisterna magna. On the 7 th day after subarachnoid hemorrhage, two groups of animals were sacrificed to observe the change of hematoma volume and brain water content (index of cerebral edema) in subarachnoid space. The experimental results are as follows: the gross observation after dissecting the brain tissue of the rat shows that: the amount of skull base hematoma of the rats in the novel artificial cerebrospinal fluid flushing group after 7 days of subarachnoid hemorrhage is obviously reduced compared with that of the control group (shown in the attached figure 2). Meanwhile, the cerebral edema of the subarachnoid hemorrhage animals 7 days after the novel artificial cerebrospinal fluid flushing is obviously relieved, and the average brain water content (76.9% + -1.9%) of the flushing group is obviously reduced (p is less than 0.05) compared with that of the control group (79.3% + -2.3%) (figure 3). In addition, no significant complications were observed in the animals following the novel artificial cerebrospinal fluid flush treatment, indicating that its use is safe.
Claims (3)
1. An artificial cerebrospinal fluid comprises colloidal gold with particle size of 5-25 μm and concentration of 232.4 + -38.3 mg/L, sodium chloride 6-7g/L, potassium chloride 0.2-0.3g/L, calcium chloride 0.3-0.4g/L, sodium bicarbonate 1.5-2.5g/L, magnesium chloride 0.2-0.6g/L, glucose 0.5-0.8g/L, disodium hydrogen phosphate 0.3-0.5g/L, and double distilled water as solvent.
2. The artificial cerebrospinal fluid of claim 1, wherein the colloidal gold is prepared by the following steps: the gold-plated steel wire rope is prepared by reacting chloroauric acid with trisodium citrate, wherein the mass concentration of the chloroauric acid is 1%, and the concentration of the trisodium citrate is 0.0025%.
3. The artificial cerebrospinal fluid of claim 2, wherein the temperature of the reaction between the chloroauric acid and trisodium citrate is 95 ℃ and the reaction time is 15 min.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201810020569.2A CN108310008B (en) | 2018-01-09 | 2018-01-09 | Application of colloidal gold in preparation of artificial cerebrospinal fluid reagent |
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| CN201810020569.2A CN108310008B (en) | 2018-01-09 | 2018-01-09 | Application of colloidal gold in preparation of artificial cerebrospinal fluid reagent |
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| CN111214486A (en) * | 2020-02-28 | 2020-06-02 | 西安交通大学医学院第一附属医院 | Magnesium-rich artificial cerebrospinal fluid and preparation method and application thereof |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6500809B1 (en) * | 1999-11-12 | 2002-12-31 | Neuron Therapeutics, Inc. | Hyperoncotic artificial cerebrospinal fluid and method of treating neural tissue edema therewith |
| CN102018724A (en) * | 2010-11-30 | 2011-04-20 | 尚爱加 | Preparation method of medical artificial cerebrospinal fluid and application thereof |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6500809B1 (en) * | 1999-11-12 | 2002-12-31 | Neuron Therapeutics, Inc. | Hyperoncotic artificial cerebrospinal fluid and method of treating neural tissue edema therewith |
| CN102018724A (en) * | 2010-11-30 | 2011-04-20 | 尚爱加 | Preparation method of medical artificial cerebrospinal fluid and application thereof |
Non-Patent Citations (1)
| Title |
|---|
| Learning to breathe:control of the inspiratory-expiratory phase transition shifts from sensory- to central-dominated during postnatal development in rats;Mathias Dutschmann,et al;《The Journal of Physiology》;20090824;第587卷(第20期);4931-4948 * |
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