Colloid solution refers to a certain size of solid particles of drugs orPolymer compoundA solution dispersed in a solvent.The particle size of its dispersion system is generally between 1~100 nm. Most of the dispersion medium is water, and a few is non-aqueous solvent.Solid particles are dispersed in solvent as multi-molecular aggregates (colloidal particles) to formPolyphaseUnevenDispersion system(Hydrophobic glue) The macromolecular compound is dispersed in the solvent in the form of a single molecule to form a single-phase homogeneous dispersion system (hydrophilic glue).This kind of solution has its unique properties, which are different from low molecular weightDispersion system--True solution(The particle size of the dispersed phase is less than 1 nm), which is also different from the coarse dispersion system -Suspension(The particle size of dispersed phase is greater than 100 nm).Colloid solutions are widely used in pharmaceutics, especially in animal and plant drugs.
Colloid solution refers to a certain size of solid particles of drugs orPolymer compoundA solution dispersed in a solvent.The particle size of its dispersion system is generally between 1~100 nm. Most of the dispersion medium is water, and a few is non-aqueous solvent.
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Colloid pressColloidal particlesThe affinity with dispersant can be divided into hydrophilic colloid and hydrophobic colloid. When the dispersant is water, it is called hydrophilic colloid and hydrophobic colloid.The system formed by colloidal dispersion in dispersion medium is called colloidal solution. Colloidal aqueous solution is widely used in traditional Chinese medicine pharmacy.
Colloid compounds (protein and othersPolymer compound)Ofmolecular structureIt contains many hydrophilic groups and can interact with water molecules.After hydration, the particles disperse in the water in a molecular like state to form a hydrophilic colloidal solution.Such as animal glue juice (donkey hide gelatin, antler gelatin, gelatin and bone glue, etc.), aqueous solution of enzymes (pepsinTrypsin, lysozyme, urokinase, etc.) and other biochemical agents containing proteinCellulose derivatives, natural polysaccharide, mucilage and gum, etc., syntheticdextran、PolyvinylpyrrolidoneThe colloidal solution formed after encountering water belongs to this category.The majority of hydrocolloids are polymer compounds, so the hydrocolloid solution is also called polymer aqueous solution.With the increase of the number of non-polar genes, the hydrophilicity of colloid decreases, while the affinity for semi polar and non-polar solvents increases. When colloidal particles are dispersed in these solvents, the solution formed is called hydrophilic colloid solution or polymer nonaqueous solution, such as corn glutenEthanol solutionOr acetone solution.
hydrophobic colloid
Hydrophobic colloidal solution, also known as sol, is a dispersion system formed by the dispersion of particles (1~100nm) gathered by multiple molecules in water.The hydration between particles and water is very weak, so there is an obvious interface between them and water, so the sol is a micro multiphaseDecentralized system, with coalescence instability.The surface of the sol particles has a very thin electric double layer structure, which contributes to the stability of the sol.Hydrophobic colloids are rare in pharmaceutical formulations, but they are often encountered in the preparation of traditional Chinese medicine.For example, during the preparation of glue, a small amount of alum is added to the glue juice to precipitate and remove the fine solid particles (dust and other impurities with particle size of 1-100nm) in the glue juice.
Protective colloid solution
Hydrophobic colloidal solution, as described above, has colloidal particlesEasy polymerizationFormation of large particles and instability of precipitation.Add a certain amount to the hydrophobic colloidal solutionHydrophilic colloidal solutionIt makes the surface of colloidal particles absorb a layer of hydrophilic colloid, hinders the mutual contact between colloidal particles, and increases the stability of hydrophobic colloid. This effect is called colloidal protection, and this type of colloid is called protective colloid.From this point of view, the glue juice in the above mentioned glue preparation can also be regarded as protective colloid because solid particles will absorb some glue liquid;Where there are gums (donkey hide gelatin, antler gum, etc.
Gel and dry glue
SomeHydrophilic colloidal solution, such as gelatin aqueous solution, donkey hide gelatin, antler gum and other aqueous solutions, agar aqueous solution, etc., which are viscous flowing liquids under warm conditions.However, when the temperature decreases, the chain dispersed polymer forms a network structure, and the dispersion medium water is all contained in the network structure, forming a non flowing semi-solid, called gel, and the process of forming gel is called gelation.2% gelatin aqueous solution can form gel at a certain temperature;However, aqueous solutions such as donkey hide gelatin require a higher concentration to form gel, because part of the collagen is hydrolyzed.When the gel is placed at an appropriate temperature, it loses the moisture inside the network structure and forms a solid gel block, which is called xerogel.The xerogel can be dissolved in water to form a hydrophilic colloidal solution. If the xerogel is crushed, the gel dissolves quickly and forms a hydrophilic colloidal solution in warm water.The whole process of preparation and application of traditional Chinese medicine glue actually makes collagen or denatured product dissolve in water to form hydrophilic colloid solution;It is concentrated to a certain concentration, and then cooled to form gel;Cut the gel into flakes and dry them to form dry gel.
Thixotropic glue solution
A few colloidal solutions, such as the colloidal solution formed by aluminum stearate dispersed in vegetable oil, gradually become semi-solid gel when standing at a certain temperature, and then become mobile colloidal solution when shaking.This property of colloidal solution is called thixotropy, and this colloid is called thixotropic glue.Thixotropic gum can sometimes be encountered in suspension eye drops or injections.
characteristic
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Understand and use colloidal properties to prepare stableColloid solution agentAnd the process used as other dosage forms is very important.For example, the purification of protein containing products by salting out and dialysis, and the impurity removal by ethanol precipitation commonly used in Chinese herbal medicine injections, are all related to the colloidal properties.Since it is difficult to distinguish the properties of solution and polymer solution, the comprehensive characteristics of colloidal solution are described as follows:
Colloidal particle size
It is between true solution and coarse dispersion system, so colloidal bath is different from true solution.It has a certain viscosity, its colloidal particles have a small diffusion speed, can pass through the filter paper but not through the semi permeable membrane, and has little influence on the boiling point of the solution, the freezing point, the vapor pressure and the osmotic pressure.Because of this characteristic, dialysis and electrodialysis can be used to purify colloid, and ultracentrifugation can be used to separate colloidal particles.
Brownian motion
Colloidal solutions are also different from coarse dispersion systems.It is a dynamic stable system with small settling speed.Therefore, the colloidal solution can be kept for a long time without precipitation.However, in addition to the strong Brownian motion in the colloidal system, due to the high degree of dispersion, the specific surface and surface energy of colloidal particles are large, and there is a spontaneous trend that colloidal particles merge to reduce the surface energy.Therefore, the colloidal solution is also a thermodynamic unstable system, which often coalesces, causing the colloidal solution to appear during long-term storageAging phenomenon。
Scattering
When the strong light passes through the solution, countless shining light spots can be seen in the dark room on the side where the light passes.Like sunlight from the windowIn holeShot into a dusty darkroom.This phenomenon is calledTindall effect。Because the intensity of the scattered light is related to the size of the colloidal particles (when the concentration of the solution is constant), the change of the dispersion of the colloidal solution can be inferred from the change of the intensity of the scattered light to study the stability of the colloidal solution.At the same time, the scattered light intensity can be used to determine its concentration, that is, turbidity analysis. The instrument used is an opacimeter.Many colloidal solutions are colored because they absorb light of different wavelengths.For example, the albumen silver solution is dark red.The smaller the colloidal particles, the more short wave (blue, purple) light absorbed, so the size of colloidal particles can also affect the color of products.For example, when colloidal gold ions change from small to large, the color of solution changes from red to purple and blue.
Particle electrification
The electrification of colloidal particles can be proved by the electrokinetic phenomenon of colloidal liquid under the action of electric field, in which the dispersed phase particle (colloidal particle) moves towards the electrode with opposite symbol, while the medium moves towards the other electrode.
It is believed that the charging of colloidal particles has a double electric layer structure.That is, the colloidal particles absorb an ion in the electrolyte to formAdsorption layer, hetero ions are distributed near the surface of colloidal particlesdiffusion layerIn this wayElectric double layer。There ispotentialThe difference is called two potential.The stability of colloid depends on the magnitude of two potential.
Understanding the positive and negative charge of colloid helpsColloid solution agentReasonable preparation.asPepsinPepsin in the mixture is known to be positively charged in acidic environment, while fibrous filter materials such as ordinary filter paper and gauze are negatively charged, so filtering should be avoided when preparing the mixture to avoidElectric neutralization, so that pepsin can be separated on the filter paper to reduce the efficacy.
stability
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The stability of colloidal dispersion system mainly depends on hydration and the charge of colloidal particles. The stability of hydrophilic and hydrophobic adhesives are discussed as follows:
Stability of hydrocolloids
Mainly relying on its strengthSolvationHydration layer with colloidal particles.Because the hydration layer around the colloidal particles prevents the particles from coalescence, the thicker the hydration layer, the greater the stability.Therefore, all factors that can destroy the hydration layer of colloidal particles can cause the instability of hydrophilic colloid.For example, add a small amount of hydrocolloidelectrolyteIt will not cause condensation due to the ion action of opposite charge.Once the hydration layer is removed and hydrophobic colloidal particles are formed, it is easy to precipitate on the condensation surface.for exampleGum arabicAfter ethanol is added to the gel solution such as agar for dehydration, the colloidal particles lose their hydration layer and coagulate when they encounter cations.Similarly, if a large number of electrolytes are added to the hydrocolloid, because the electrolyte ions have strong hydration properties, the hydration layer of the colloidal particles will be removed after the addition, which will also cause condensation and precipitation.This action is calledSalting out。
Add a large amount of ethanolacetone, syrup and other dehydrating agents can alsoSolvationThe hydrated layer of the colloidal particles is damaged and dehydrated to separate out.Or although no precipitationelectrolyteIt is more susceptible to salting out.
Hydrophilic colloid occurs if it has been affected by light, heat, air, etc. for a long timeChemical changeWhen the change product has a small solubilityCondensation phenomenon。If the colloidal solution is added with immiscible liquid and then powered on, or vibrated violently, or boiled or frozen, partial or total colloidal particles can coagulate.Ultraviolet and X-ray can also make the glue solution sensitive to electrolyte.
Stability of hydrophobic colloid
Since the colloidal particles cannot be hydrated, they are mainly stabilized by carrying the same charge on the surface and repelling each other.But hydrophobic colloidal particles onlyAdsorption layerOnly when the adsorbed ions and some hetero ions exist can they be charged and have a certain degree of stability.If the hydrophobic colloid (generally refers toSol)Medium and small amountelectrolyteIf the colloid is removed by dialysis, it will lose its charge, and the colloid will coagulate and precipitate.Therefore, there must be a small amount of electrolyte in the colloid as a stabilizer, whose positive and negative charges form a double layer structure of colloidal particles, so that hydrophobic colloidal particles can carry a certain amount of charge to achieve a certain degree of stability.The amount of electrolyte must be appropriate. If too much electrolyte is added, with the increase of the concentration of added ions, the original distribution ofdiffusion layerThe opposite ions in the diffusion layer which is far away from the pre adsorption layer are squeezed into the adsorption layer, so that the opposite ions in the diffusion layer which is far away from the pre adsorption layer are close to the adsorption layer, which gradually thins the diffusion layer and reduces the potential that plays a stabilizing role.When the potential drops to the critical value, the colloidal particles will coagulate.soSolIt is sensitive to electrolyte.
preparation
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Preparation of Hydrophilic Colloids[1]
The preparation of hydrophilic sol must first go through the swelling process.Swelling refers to the process in which water molecules infiltrate into the pores of hydrophilic sol compounds, hydration with hydrophilic groups and volume expansion, resulting in the filling of polymer pores with water molecules. This process is called limited swelling.
Due to the existence of water molecules in the pores, the intermolecular force is reduced, and the swelling process continues.Finally, the compound is completely dispersed in water to form a hydrophilic sol, a process called infinite swelling.
Preparation of Hydrophobic Colloids (Sols)[1]
1. Dispersion method
Dispersion method The process of dispersing coarse drug particles into a range of sol particle sizes.
(1) Mechanical dispersion method: colloid mill is usually used for preparation
(2) Colloid method: the method of re dispersing the coarse particles gathered into sol particles
(3) Ultrasonic dispersion method: use the energy generated by ultrasonic wave above 20kHz to disperse the coarse particles into sol.
2. Coagulation
(1) Physical coagulation method: Sol is prepared by changing the dispersion medium to make the dissolved drug precipitate microcrystals in the bad solvent.
(2) Chemical coagulation method: Sols are prepared by chemical reactions such as oxidation, reduction, hydrolysis and double decomposition.