Chinese medicine extraction technology
Chapter microwave and ultrasonic extraction
Microwave extraction (ME) , also known as microwave-assisted extraction, microwave and conventional solvent extraction Combination an extraction method is the use of microwave energy to improve the extraction efficiency of a new technology -assisted extraction .
Features: 1, fast and efficient 2 , uniform heating 3 , selective four , biological effects
Microwave (MW) , also known as ultra-high frequency electromagnetic waves, wavelength : 1mm ~ 1m, Frequency : 0.3 ~ 300GHz, industrial and home use : 2.45GHz ( to prevent interference to radio communications ) .
Microwave having mutually perpendicular electric and magnetic fields , electric dipole by synchronizing rotation and ionic conductance heating effect .
Factors: 1 , the microwave power of the solvent 2 3 4 extraction time , temperature 5 , the matrix material 6 , the cooling time
Ultrasonic extraction (UAE) is the use of ultrasonic waves to the mechanical effect of the cavitation effect and the thermal effect , by increasing the velocity of the media elements , increasing the penetration of the medium to extract the active ingredients of Chinese medicine approach.
As the ultrasonic frequency increases , the extraction efficiency is not be significantly increased, but to prevent decomposition of active ingredient . Frequency ultrasound is generally used for the extraction of alkaloids .
Features : 1 , extraction without heating , to avoid the traditional extraction method requires high-temperature heating caused by the destructive effects of the active ingredient , particularly suitable for the extraction of heat sensitive materials . 2, the extraction efficiency is high. 3 , saving solvents. 4 , does not affect the activity of the effective component . 5 , extract the active ingredient content, will help further purification. 6 , saving energy.
Factors: 1 , solvent 2 , ultrasonic frequency 3 , extraction time 4, the temperature 5 , herbs organizational structure 6 , ultrasonic cohesion mechanism
Chapter Supercritical Fluid Extraction
Supercritical fluid extraction in the supercritical temperature conditions , changing the pressure to change the polarity of the supercritical fluid and other features can be extracted components of different polarities , which is called a supercritical fluid extraction method to extract .
The main features of supercritical fluids : both a high-density liquid state , but also has a gaseous possess low viscosity and strong permeability , the diffusion coefficient than 100 times larger than ordinary liquid .
Supercritical carbon dioxide (SF-CO2) is most commonly used , has a lower critical pressure and critical temperature characteristics or advantages :
1 , operable at room temperature , the majority of chemically inert material , can effectively prevent the heat-sensitive composition and the chemical instability of the heat damage and oxidation ;
2 , stable, colorless, odorless , non-toxic , extract no residue, no dissolved pollution ;
3 , cheap, easily made into high-purity gases , nonflammable , safe to use ;
4, the extraction speed, greatly shorten the production cycle , low operating costs , and good selectivity .
Nature ( about ) : 1 , the density of the density with SF-CO2 pressure and temperature changes, the variation of characteristics:
1 ) near the critical point , small changes in pressure and temperature , the density of the fluid will significantly change ; 2 ) in the supercritical region , the density at 150 ~ 900g/dm3 large range. Its density is proportional to its ability to dissolve the basic , small changes in density can cause significant changes in solubility .
2, the transfer performance SF-CO2 on solute transport rate was significantly higher than the liquid .
3 , SF-CO2 solubility with the solubility of polar compounds increases.
Rules: 1 ) a lipophilic , low-boiling hydrocarbons and dissolved ability lipid compounds , such as volatile oils, hydrocarbons, esters , ethers , lactones , and epoxy compounds . 2 ) the compounds of polar groups such as hydroxyl , carboxyl , the more the smaller solubility . 3 ) the higher molecular weight compounds , the harder it is extracted homologues solubility decreases with increasing molecular weight .
SF-CO2 extraction factors ( discussed )
1, the medicine particle size smaller the larger the total surface area , the faster the mass transfer of solute molecules in contact with the SF-CO2 more opportunities , increased extraction , extraction speed, extraction operation cycle can be shortened . But the size is too small, easily dissolved impurities herbs , affecting product quality.
2, the pressure in the critical state, the extraction temperature is constant , small changes in pressure will cause drastic changes in fluid density , fluid density , the stronger the greater the solubility , the shorter the time required for extraction , extraction of the more complete .
3, the temperature of temperature on the SF-CO2 solubility with two sides. On the one hand , a certain pressure , the temperature rises , the diffusion speed extracts , volatile , is advantageous to extraction ; other hand, increasing the temperature , SF-CO2 density is reduced, decreased solubility of the fluid , the extraction negative.
4, CO2 flow CO2 flow rate increases, the effect would SFE-CO2 produced both positive and negative effects .
5 , entrainer is added entrainer increased SF-CO2 fluid solubility of polar components , the extraction process may be relatively lower pressure .
6, the extraction time when the temperature , pressure and fluid flow rate and other conditions are fixed , the extraction time extension , the extraction rate of increase, but prolonged extraction, may increase the solubility of the impurity dissolution of smaller , but also increase the cost .
SF-CO2 extraction technology to extract active ingredients in traditional Chinese medicine in the application of the advantage
1 , the extraction speed, short production cycle 2 , the extraction ability, extraction rate 3 , simple process , easy operation 4 , low operating temperature , high product quality
Extraction range : alkaloids, phenylpropanoid phenols, quinones and its derivatives , essential oils, stickers category , saponins and polysaccharides .
Chapter microcapsules
Microcapsules takes advantage of natural or synthetic polymer material ( carrier material ) as the capsule , the solid or liquid medicine ( including the additional agent) wrapping the film - shell of the dosage form .
Chinese microencapsulated features: 1 , cover the bad smell and taste of Chinese medicine 2, to improve the stability of three traditional Chinese medicine , Chinese medicine in the stomach to prevent inactivation or reduce stomach irritation 4 , the liquid medicine used to facilitate storage of solid flower 5, to improve bioavailability 6 , may be prepared as slow release or positioned release 7 , the medicine concentrated in the target carrier material of the general requirements: 1 ) stable 2 ) a suitable release rate 3 ) non-toxic, no irritation 4 ) does not affect the pharmacological effects of traditional Chinese medicine and determination 5 ) have a certain strength and plasticity , can be completely encapsulated or adsorbed loading 6 ) has to meet the requirements of viscosity, penetration , hydrophilicity, solubility , biodegradable natural polymer materials and other characteristics : the most commonly used carrier materials , characteristics : a stable , non-toxic as the ball or the film is good ( gelatin , gum arabic, alginate , chitosan ) semi- synthetic polymer materials as: Department of cellulose derivatives , features: toxicity, viscosity, it can become a salt by salt solubility increases. ( Salt of carboxymethyl cellulose , Cellulose acetate , ethyl cellulose (EC), methyl cellulose (MC), hydroxypropyl methyl cellulose (HPMC))
Synthetic polymer materials : There are two types of bio- degradable and non-degradable . Organisms which are not biodegradable , and is not pH value : the polyamide, silicone rubber ; organisms which are not biodegradable , but can be dissolved in a certain pH conditions : the polyacrylic acid resins , such as polyvinyl alcohol ; Biodegradation: polycarbonate , poly amino acids , polyglactin (PLA), lactide - glycolide copolymer (PLGA), polylactic acid - polyethylene glycol copolymer embedded off (PLA-PEG), e- caprolactone and lactide copolymer and so on. Its characteristics: non-toxic, good film , high chemical stability , can be used for injections.
Preparation of microcapsules
1, the physical chemistry
1 ) Single- condensation method 2 ) complex coacervation 3 ) solvent - non- solvent method 4 ) changing the temperature France 5 ) Drying in liquid 6 ) Emulsion - crosslinking 7 ) co-precipitation method
2 , mechanical France
A ) spray drying method 2 ) spray congealing method 3 ) air suspension 4 ) supercritical fluid method
Single- phase separation coacervation method is a method commonly used in the cross- body material ( gelatin , CAP, chitosan, sodium alginate, albumin , etc. ) coagulant was added to reduce the solubility of the polymer material into a bag or condensed the method into a ball .
Principle: Chinese material dispersed in a gelatin solution and then adding coagulant ( can be strongly hydrophilic electrolyte such as sodium sulfate solution, or strongly hydrophilic non- electrolytes such as ethanol ) , the gelatin molecule membrane hydration water molecules and cohesion binding agents , to reduce the solubility of gelatin , to form intermolecular hydrogen bonds , and finally precipitated from the solution and condensation to form condensation sac or balls.
Coacervation method is to use two oppositely charged polymer composite material as carrier material , under certain conditions, the crosslinking cysts were condensed into a pouch loading method .
Principle: pH of the solution was adjusted to the isoelectric point of the gelatin to make the belt less positively charged , and the time is still negatively charged gum Arabic , because charges attract each other to form cross -linked complex of positive and negative ions , and condensed into a lower solubility capsule, diluted with water , formaldehyde crosslinking , washed formaldehyde , ie.
Composite material can be used with a positively charged and negatively charged gelatin, gum arabic ( or polysaccharides such as CM or CAP ) , polylysine- alginate , alginate and chitosan , alginate and albumin , albumin and gum arabic .
Factors affecting particle size 1, the loading of size 2 , the amount of carrier material 3 , Preparation 4 , the stirring rate was prepared 5 , 6 concentrations of additives , the viscosity of the carrier material with
Chapter liposomes Liposomes with the class
Liposomes are the phospholipids and other amphipathic substance is dispersed in water , the lipid bilayer membrane encapsulating drugs , one or more layers formed by concentric spherical body , meaning that the lipid bilayer of the water inside closed vesicle phase .
Features: showing cell affinity and Histocompatibility
1 , targeting [ passive ( natural ) targeting , active targeting , physical and chemical targeting , transfer targeting ] 2 , expanding herbs 3 , sustained or long-term nature of liposomes as drug carriers special , can improve the selection of drugs on target and thus reduce the dose , reducing adverse reactions.
Liposomes are membrane-forming material and the additional agent. The film-forming material is its main phospholipids , phospholipids including lecithin, phospholipids, soybean phospholipids and synthetic phospholipids .
Additional agents are cholesterol, polyethylene glycol , a stabilizer and gels and the like . Phospholipid liposomes membrane skeleton , the amphipathic substance , the hydrophilic and lipophilic groups.
Factors affecting liposome
1 , affecting liposome particle size and its distribution factors, such as preparation method
2, the encapsulation efficiency of the factors affecting the nature and concentration of a pharmaceutical drug electrically b (if electrical and drug liposomal membrane and opposite by its high encapsulation efficiency ) c Relative molecular mass drugs ( drugs relative molecular mass of large high encapsulation efficiency )
3 , affecting the stability of liposome leakage rate factors and a temperature b lipid membrane composition leakage rate = product during storage after a certain time leak into the medium dose / products in the encapsulation of the drug before storage * 100%.
Class Liposomes are non-ionic surfactants consisting of a cholesterol vesicles purified single-or multi-layer , also known as non-ionic surfactant vesicles may also be referred to as non-ionic liposomes, is a novel pharmaceutical carrier.
Features : 1, expanding the scope of the drug entrapped 2 , 3 to improve the effect of drugs , to improve stability 4 , 5 can be adjusted and flexibility , can have a variety of delivery channels 6 can be set multiphase drug
Chapter nanoemulsion with multiple emulsion preparation
Nanoemulsion is the diameter of the droplet 10 ~ 100nm dispersed in another liquid in the form of a transparent or translucent colloidal dispersion system . ( By autoclaving or centrifugation is not hierarchical )
Multiple choice : nanoemulsion formation is a spontaneous process . Nanoemulsion from the aqueous phase , oil phase , emulsifiers and coemulsifiers four parts, which oil emulsifier is generally 20% -30 % , while the average milk emulsifier generally lower than the amount of oil 10%. To produce a surfactant compatibilizer known solubilizing substance is called compatibilizer quality compatibilizer .
Micelle is a colloidal solution , the excess of surfactant in water, the formation of self-assembly , the core of a hydrophobic , a hydrophilic shell.
Double emulsion was further emulsified by the ordinary emulsion formed complex emulsion system , also known as multi-layered milk . There W / O / W type and O / W / O type .
Auto -emulsion containing a drug , an emulsifier, sometimes with isotropic and lipid emulsifier mixture in water or a mild shaking automatically form a transparent or translucent O / W type emulsion , the particle size can be small 5-140nm, can be large to the micron level , which automatically either for the preparation of the nanoemulsion emulsion , submicron emulsion , can also be used to prepare ordinary milk . Association of surfactant molecules to form micelles with the minimum concentration is called the critical micelle concentration (CMC)
Milk into milk affecting complex factors: 1 , the choice of two oil phase , emulsifier impact 3 -phase volume fraction 4, the mixing rate and mixing time 5 , 6 ultrasound effects , including the nature of the drug load ( short answer )
Chapter solid dispersions
Solid dispersion (SD) refers to drugs, in particular highly dispersed insoluble solid pharmaceutical physiological activity in the absence of a carrier material to form a solid dispersion. Size 1-100nm solid dispersion characteristics
Advantages : You can use different types of carrier material of the drug in a highly dispersed state of the drug required to achieve different purposes. 1 , the hydrophilic polymer insoluble carrier material to increase drug solubility and dissolution , thus improving the bioavailability of the drug ; 2, the use of insoluble polymeric carrier material to delay or control drug release ; 3 , the use of enteric polymer controlling drug carrier material positioned in the small intestine release ; 4, the use of the carrier material encapsulated in effect , delaying drug hydrolysis and oxidation , cover the unpleasant odor and irritation , the liquid pharmaceutical solids and so on.
Disadvantages : long storage may be changed pharmaceutical polymorphs , recrystallization of the crude crystals , drug dissolution was reduced by aging , to some extent, affect the clinical applications of solid dispersion .
Solid dispersion prepared from : 1 , 2 melting method , the solvent method 3 , solvent - melting method 4 , 5 grinding method , a spray drying method
Inclusion refers to a group or part of drug molecules through the inclusion technique into another compound molecular structure of the cavity formed within a class of non- chemically distinct forms cyclodextrin inclusion complexes in the application of Chinese medicine formulations major role ( or cyclodextrin Features )
Short answer or essay questions
1, increase drug solubility , increased bioavailability 2 , 3 to improve the stability of the drug , mask bad odors , reducing irritation , reducing adverse reactions 4 , solidification of liquid medicine , easy preparation processing 5 , 6 release rate adjustment , with separation and determination of the drug
Chapter VII of the oral sustained-release , controlled-release and delayed-release formulation of new
Means the provisions of sustained-release formulations release medium , the required non- constant slowly release the drug , and its comparison with the corresponding general formulation , dosing frequency reduced by half or more than ordinary preparations administered more frequently than normal preparations decreased, and can significantly increased patient compliance preparations .
Means the provisions of controlled release formulations release medium , as required constant or nearly constant slow release of the drug , and its comparison with the corresponding general formulation , dosing frequency reduced by half or more than ordinary preparations dosing frequency decreased than ordinary preparations , the plasma concentration is more stable than the sustained release formulation , and can significantly increase patient compliance preparation .
Delayed release formulations after administration does not mean immediate release drug formulations , including enteric preparation , colon and pulse preparations and other preparations .
Compared with the ordinary preparations , slow and controlled release formulations which features or advantages ?
A: 1 , easy to use 2 , reduce the " peak " phenomenon 3 , 4 adverse reactions , efficacy play well
Gastric motility mainly in two forms : full stomach tonic contraction and creep (ru) move. Food from the stomach into the duodenum is called gastric emptying .
Factors affecting gastrointestinal absorption ?
A: 1, the physicochemical properties of two drugs , gastrointestinal fluid composition and properties of three , under the impact of four gastric emptying , gastrointestinal motility effects 5 , the first pass effect
Learn : ethyl cellulose (EC): non-toxic , non- pharmacological activity , ideal insoluble carrier material , chemically stable , alkali , salt solution . At higher temperatures , sunlight or ultraviolet light, easily oxidized decomposition. Incompatibility with paraffin . Soluble in ethanol , benzene, acetone and other organic solvents
Hypromellose (HPMC): white to white fibrous or granular powder flow , dissolved to form a colloidal solution in water , insoluble in ethanol , chloroform and ether, dissolved in methanol and a mixed solvent of chloroform .
Chitin : polysaccharide polymer material has good biocompatibility , non-toxic , chemically stable , non- pharmacological activity , usually white or light yellow powder.
Intragastric floating sustained-release tablets is the application of hydrodynamic equilibrium system (HBS) principle , the use of hydrophilic polymer materials, low-density materials mixed with the drug compressed into tablets .
May consider floating sustained release tablets made ​​from the stomach of the drug which ?
A: 1, mainly absorbed from the stomach acidic drugs 2 , play a role in the stomach antacid drugs 3, the best parts of the upper small intestine absorption of the drug 4 , drug transferred from the stomach to the intestines , leaving due to pH changes greatly reduced solubility of the drug .
Impact osmotic pump (beng) tablets drug release factors 1, 2 membrane osmotic pressure difference inside and outside , coated membrane water permeability 3 , release hole size
Enteric preparation : pH -sensitive and delay -type
Colon preparation advantages: 1, can play a role in systemic treatment , especially peptides and proteins to improve macromolecular drugs oral bioavailability of two , a special treat colon related diseases 3 , not only positioning therapeutic effect, but also to meet the hour pharmacology need for asthma, arthritis and other diseases affected by temporal rhythm has important therapeutic implications .
Vivo experimental studies ( understanding 229 )
Chapter VIII of the new formulation of transdermal drug delivery
Transdermal refers to drugs with stickers, paint , paint , dressing , washing , immersion , smoked, ironing (yun) and iontophoresis other methods applied to the skin through skin absorption or retention agents in order to play local or systemic drug therapy the role of a method of administration .
Chinese medicine transdermal refers to the theory of Chinese medicine Chinese medicine prescriptions under the guidance of a single flavor or compound by extraction , separation and purification of the resulting effective components and parts or extracts through rational formulation design and craftsmanship made ​​of appropriate dosage forms , enabling the medicinal ingredient at a constant rate ( or nearly constant rate ) through the skin , absorption into the systemic circulation , resulting in local or systemic therapeutic effect of traditional Chinese medicine preparations.
The advantage of a transdermal drug delivery systems , to avoid gastrointestinal environment and hepatic first- pass effect of drugs interfering with the destruction of two effects , can avoid the phenomenon of peak plasma concentration , to maintain a stable blood concentration , thereby enhancing drugs biological utilization 3, to provide a longer duration of action can be expected to reduce the number of drugs 4 , reducing drug toxicity and adverse reactions.
Skin: There epidermis, dermis and subcutaneous layer.
Drug scalp ways: First, through the stratum corneum and activity of the epidermis, the dermis is spread to the capillary walls absorb the monarch as epidermal circulation pathways ( major route )
The second is absorbed through the skin appendages , namely through the hair follicles, sebaceous glands and sweat absorption.
Affecting drug percutaneous absorption factors:
A drug factors: 1 ) the relative molecular mass of two drugs ) Drugs oil / water partition coefficient and solubility 3 ) the form of the drug molecule 4 ) the melting point of drug
2 , delivery system factors: 1 ) the composition of the two delivery systems ) penetration enhancers selection 3 ) Composition of traditional Chinese medicine
3 , the skin factors: age , sex , skin lesion , and normal and pathological states will result in different skin permeability differences.
Penetration enhancers (PE) is a reversibly change the skin barrier function of the stratum corneum without damage to any living cells , to enhance the transdermal drug ability to improve transdermal drug substance amount .
Commonly used transdermal absorption enhancers : alcohols , fatty acids and fatty alcohols, Azone , terpenes .
Physical transdermal penetration method : 1, 2 iontophoresis , ultrasound penetration enhancers 3.Laser promote through 4 , electroporation transdermal penetration 5 , microneedle transdermal penetration
Babu medicinal ointments means extracts, herbs , and chemical drugs , or with a suitable hydrophilic matrix after mixing , coating on the backing material paste made ​​of plaster .
Babu ointment advantages: 1 , matrix and drug compatibility , and apply a wide range of drug loading capacity, suitable for medicine multicomponent , large doses of medication . 2 , the matrix water , moisture , and can promote the skin and the role of water is conducive to transdermal drug absorption and improve bioavailability. 3 , close to the comfortable , good air permeability, perspiration resistance , repeatedly exposing stickers no pain , no residue , no contaminated clothing . 4 , skin irritation and allergic small, and the dose can be adjusted easily accessible area , improve patient compliance and safety. 5, the production process does not use gasoline and other organic solvents , to avoid environmental pollution, comply with environmental requirements .
Chapter IX mucosal administration of new formulations
Mucosal administration refers to drugs ( either directly or using a suitable carrier ) in direct contact with the mucosal surface organisms , and by the epithelial cells into the tissue where a mode of administration .