Method for preparing microcapsule by high-voltage electric field encystation and low-temperature extraction and solidification

The high-voltage electric field of the low temperature suction solidifying to prepare the micro capsule method

technical field

The invention relates to a preparation movable object capable degrade portion slowly the micro capsule the novel process, relates to a high-voltage electric field to form the two low temperature suction solidifying to prepare the micro capsule said method.

background technology

Micro capsule technology develops the gift with dozens years. The people discovered of the rear wall of the material is micro capsule technology the medicine making the micro-spheres, comprising a enhance the medicine, stability to achieve the buffer device or a control device and improved biology compatibility and a merits. The natural high polymer The Cai according however for people time discovered can degrade the body, easy to the body is area, without suit for intravenous injection, hypodermic the upper layers; the micro softgel and between the human body is limited. Further arranged recent years, the people restoring high polymer The Cai and a device for biology sleeved with a degrade, and lactic acid (PLA) and a lactic acid is polyoxyethylene copolymer (PLA-PEG) and a lactic acid and hydroxyacetic acid copolymer (PLGA) are in a. Fabric with a chemical stability high, is processed at the inner degradation, which can is used for intravenous injection and a merits. And PLA and PLGA is sleeved authorized of US FDA Food Medicine Administrative for Containing the drug release carrier.

The biology degradable metals, wherein because chemical stability upper and body, and is not easy to prepare the micro capsule. The gift majority of a lactic acid (PLA) and a lactic acid hydroxyacetic acid copolymer (PLGA) biology degradable micro capsule is made of emulsifying middle method and clutch preparation method and carbon dioxide. The solve evaporating method to emulsify in the middle method of common preparation method thereof, comprising a single emulsion method (O/W and O/O) and the emulsion (W/O/W), the single emulsion's method shortcoming to the medicine the envelope rate is low, generally is 20% and. Further covered on the external (W/O/W) is further recent the years common PLGA micro capsule preparation method thereof. Comprising a hinder medicine to distribute enter the continuous is effectively, a making the envelope rate reinforcing, which is reported device for type external method for preparing the micro capsule, the envelope rate is a to reach 40%~70%. The lotion covered on the inlet of the single emulsion's method base, further however further provided with a deficiency: (1 )Is capsule release concave; seriously(2 )Is capsule of irregular, easy to the accumulation, bulking not; a(3 )Is increased emulsifying agent and active agent, the combined protein flow type easy to denaturate; (4 )Medicine's of the length phase kettle existed, envelope rate universal and a questions. External emulsifying middle method, comprising a preparation technology further - comprising to a (condensation method) and spray-drying process and carbon dioxide. Partition () is a micro capsule particles method of preparing is easy to reunite, a hard real production, and application thereofFurther of the spray-drying process, although can preparing PLA and PLGA micro capsule successfully, a gap of the preparation process, wherein the capsule can adhere the atomization of water extractor's wall; the component to atomize is in a transition of the product is massively, and making the product reunion.

The invention

The problem of the objective of the present invention is overcome of the existing technology with, claims a high-voltage electric field to form the two low temperature suction solidifying to prepare the micro capsule method for preparing the biology is a degrade the material of the buffer device is capsule. Combination the high-voltage electric field method and low temperature extracting method, around the movable preparation device is a degrade the micro capsule the novel process.

The invention's technical solution, a high-voltage electric field of the two low temperature suction solidifying to prepare the micro capsule method, wherein the steps: 1st, Connected to The hanging Bicai the acetone liquid the core material(1%~6% (W/V)]; 2nd, Wherein the suspension through a high-voltage electric field micro capsule forming device (ZL00218100.2); the device for the electric field intensity and a propeller function; the screw speed through the regulating electric field distance and ejecting the voltages, the adjusting syringe lower ends and liquid nitrogen liquid level, making the different particle size of the liquid ball; 3rd, Globule liquid inlet adjusting device with one of 196℃ liquid nitrogen container of the liquid ball solidification of the ball; 4th, So that the container of the 60℃~-90℃ low temperature, environment of the freezing in difference between alcohol type paste agent and acetone, enables the paste agent dissolving to first; and acetone the mixing liquid the solidifying metal ball to dissolving; slowly5th, Then end of the acetone with a alcohol type paste piece layers; the polymer to produce the deposition, wherein the capsule can; solidify6th); The solidifying, wherein of the deionized water cleaning and centrifugal, the freezing and drying preservation laboratory.

The method's actual result is: Because the method of a solidifying the core plate material mixed middle of the flat micrometer balls; then end of the slow solidifying, therefore, wherein the handle is liquid tank of the tremendous pressure oil suction with washing of the shell microcyst or for producing big hole is configured the micro-spheres to release, envelope rate and carrying materials is a concave; seriouslyOn the other handle of dope the micro capsule of the solidifying layers; the micro capsule solidifying the dispersivity is good, no the accumulation. The matter the polymer starts to type from any direction, a theory of preparing of the ruler and middle of micro capsule. The characteristics to the condensation method, and lotion method and so on boss is provided with multiple superiority to a method; because of the mould of the macromolecular sedimentation and viscosity condition's the control claim of the solidifying device is high, and is not suitable for controlling, is not rod is easy to cause the micro capsule to release concave serious, comprising a accumulation, envelope rate and transferring materials to move. The method overcome with the flaws method. Moreover, a preparation process of this method for on the lower waterless condition, regarding the embedding of hydrophilic protein type sand, wherein envelope rate is provided with a high-rise. The work method of low temperature environment, and without increase the emulsifying agent and active agent, medicines with superiority of the polypeptide protein flow and a processing thermosensitive.

Brief description for drawings

Work 1 of the microprocessor capsule forming device schematic drawing, type 2 is a high-voltage electric field of the two low temperature suction solidifying to prepare the micro capsule method flow picture.

The Figure 1, 1). high pressure static field generator, 2. high pressure producer one electrode, 3. high pressure producer cathode, 4. syringe, 5. propeller, 6. bracket, 7. liquid nitrogen and 8. freeze's the ethanol detailed description of illustrated embodiments connecting joint section of micro-spheres and 9. solidifying, taking the weight of 1∶9 and insulin and implementation carrying of a lactic acid clycollic acid copolymer preparation method to the invention further describes: 1st, According to insulin: A lactic acid hydroxyacetic acid copolymer 1∶9 the proportion, the inner insulin part (3.5% W/V) and lactic acid hydroxyacetic acid copolymer acetone liquid; 2nd, Taking 200mL plastic container, glass pour the absolute ethyl of 20ml on the base; and one 196℃ liquid nitrogen wherein solidifying, a circulating liquid nitrogen to the liquid level height of needs, the connecting rod insulin and PLGA suspension through the high-voltage electric relating micro capsule forming device, and shown in work 1; the electric field intensity and a propeller function, a regulating multiple voltage (4b 3.3~3.6kV), a liquid level distance (25~35mm), and is speed, preparation of the grain size of the liquid ball.

3rd, Globule liquid inlet adjusting device with one of 196℃ liquid nitrogen plastic a glass ball liquid solidification for solid of ball.

4th, Wherein the plastic a glass is arranged 88℃ low temperature, environment of the freezing in difference between ethanol and acetone (ethanol freezing point is one 117.3℃, acetone is one 94.6℃), the ethanol paste agent inner first; and acetone solidification of the mixing liquid liquid ball and a result of closed freezing of the inner slowly.

5th, Then end of the acetone with a ethanol paste piece layers; the polymer to produce the deposition, wherein the capsule can solidify, the time of the solidifying is 2 days.

6th); The solidifying, wherein of the deionized water cleaning and centrifugal, the freezing and drying preservation laboratory.

From the mark according device and electric field voltage is 3.4kV; the liquid level distance is 35mm; the shaft is 20mm/min, the insulin micro capsule particle size of the system made of less than 200 μ m; the envelope rate is 83.2% mm, and materials is 8.82%; the buffer device is 7 days, with plastic can satisfy to the buffer device for preparing the requirement, comprising at the diabetic with a gap of the burden of the frequent injection with.