Abstract: Disclosed is a reaction device, comprising: a reactor body (100) and a supply device (200), wherein the reactor body (100) has a first end (106) and a second end (107) and is used for accommodating a reaction liquid, with a first injection port (101) being provided between the first end (106) and the second end (107), and a discharge port (109) being provided at the second end (107); and the supply device (200) is in communication with the first injection port (101) to inject a continuous phase, wherein the continuous phase directionally flows in the reactor body (100) to form or maintain a parameter gradient in the reactor body (100). By means of injecting the continuous phase into the first injection port (101) on the reactor body (100), the solution presents a certain parameter gradient on two sides of the first injection port (101) in the reactor body (100).

Abstract: The invention discloses a method for preparing embryonic microspheres, a preparation mechanism, a method for preparing microspheres and a device for preparing the microspheres. The method for preparing the microspheres comprises delivering a microsphere-forming solution to a porous membrane located in a receiving liquid through a liquid transport member, to form embryonic microspheres; delivering embryo microspheres separated from the porous membrane along a channel filled with the receiving liquid, hardening the embryo microspheres to form microspheres; and collecting the microspheres. Wherein the flow rate of output liquid from the liquid transport member is controllable, so that an amount of output microsphere-forming solution per unit time is directly controlled, thereby regulating the particle size and uniformity of the generated microspheres.

Abstract: This invention teaches a method to achieve rapid 3D printing of microneedle patches. The 3D printing method comprises a printing nozzle of multiple micro-holes and cold plate/platform on which the microneedle-supporting sheet (membrane) is placed. The solution or aqueous solution of microneedle-forming materials is printed onto the cold microneedle-supporting sheet with programed rate of injection from the nozzle and velocity of the nozzle lifting. The relationship between the injection rate and the lifting velocity determines the shape of the microneedle tips. The freshly printed microneedles on the cold sheet are dried in two ways, drying at a temperature close to the ice point of water or drying after a freeze-thaw treatment of the microneedles.

Abstract: The present disclosure disclosed a microsphere-producing process involving three integrated unit operations, 1) microspheres formation; 2) microsphere quality control; 3) post formation microsphere treatment. The first unit operation, i.e. unit operation 1) is integrated with four essential functions: forcing the particle forming materials to pass through a porous membrane to form embryonic micropsheres; enforcing the embryonic microspheres to detach the porous membrane; solidifying the embryonic microspheres; collecting and outputting the solidified microspheres. The quality control unit operation consists discrimination and ejection of oversized microspheres. The post treatment unit operation is integrated with two essential functions, smoothing the microsphere surfaces and reducing organic solvents trapped inside of microsphere matrix.

Abstract: The present invention teaches a design of apparatus using which microspheres of customizable uni-sizes may be produced through a greatly simplified process. The apparatus consists a microsphere-forming unit, a microsphere rinsing unit, and a sterile hood that isolate the other two unit within a sterilized cover. The microsphere-forming unit enables the processed of microsphere formation, solidification and collection simultaneously. The sterile hood allow the microsphere producing operation be carried out within a glove box, preventing direct contact of operator with the sterilized materials of the microspheres. The apparatus has also a refrigerator wherein the microsphere collector and final product storage are placed for extracting the solvent of microsphere-forming materials and stabilizing the final product, respectively.

Abstract: This invention teaches a method to achieve rapid 3D printing of microneedle patches. The 3D printing method comprises a printing nozzle of multiple micro-holes and cold plate/platform on which the microneedle-supporting sheet (membrane) is placed. The solution or aqueous solution of microneedle-forming materials is printed onto the cold microneedle-supporting sheet with programed rate of injection from the nozzle and velocity of the nozzle lifting. The relationship between the injection rate and the lifting velocity determines the shape of the microneedle tips. The freshly printed microneedles on the cold sheet are dried in two ways, drying at a temperature close to the ice point of water or drying after a freeze-thaw treatment of the microneedles.

Abstract: The application discloses a method to fabricate microneedle patches, comprising a) casting (painting and pasting) an aqueous polymer solution on a mold of array of micro-holes which is made of porous materials; b) sucking the polymer solution into the micro-holes by applying vacuum at the back of the mold; d) freezing and thawing the casted polymer solution to induce gelation; and e) drying the gelled polymer solution. Specifically, the present invention describes a process and composition of polymeric microneedlepatch which overcomes the limitations of existing microneedles systems and may be used for transdermal delivery system for therapeutics and other applications.

Abstract: The present invention disclosure disclosed a microsphere-producing process involving three integrated unit operations, 1) microspheres formation; 2) microsphere quality control; 3) post formation microsphere treatment. The first unit operation, i.e. unit operation 1) is integrated with four essential functions: forcing the particle forming materials to pass through a porous membrane to form embryonic micropsheres; enforcing the embryonic microspheres to detach the porous membrane; solidifying the embryonic microspheres; collecting and outputting the solidified microspheres. The quality control unit operation consists discrimination and ejection of oversized microspheres. The post treatment unit operation is integrated with two essential functions, smoothing the microsphere surfaces and reducing organic solvents trapped inside of microsphere matrix.

Abstract: A new microsphere formulation (composition) for controlled- or sustained-release delivery of therapeutic ingredient(s), mainly peptides and proteins not over 10K in molecular weight, comprises at least a therapeutic ingredient, a helping agent (such as PH sensitive agent whose solubility is a function of pH) and a biodegradable polymer. The therapeutic ingredient(s) and the helping agent are in the form of fine particles, less than 1O um in diameter, encapsulated in the polymer which forms the microsphere matrix. A method for preparing the composition comprises a step of in-situ precipitating the therapeutic ingredient(s) and the helping agent to the fine particles and successive steps for forming the microspheres. Such a microsphere formulation offers a well-controlled release profile for prolonged period and encapsulation efficiency over 95%.

Abstract: The application discloses a method to fabricate microneedle patches, comprising a) casting (painting and pasting) an aqueous polymer solution on a mold of array of micro-holes which is made of porous materials; b) sucking the polymer solution into the micro-holes by applying vacuum at the back of the mold; d) freezing and thawing the casted polymer solution to induce gelation; and e) drying the gelled polymer solution. Specifically, the present invention describes a process and composition of polymeric microneedlepatch which overcomes the limitations of existing microneedles systems and may be used for transdermal delivery system for therapeutics and other applications.

Abstract: This invention discloses a novel microneedle system, phase-transition microneedles (PTM), of which the microneedles formed of hydrophilic polymers are swelling but insoluble when absorbing water due to their internal cross-linked network through microcrystalline domains functioning as cross-linking junctions. The microneedles are sufficiently hard to penetrate the epidermis of the skin at dry state, but are converted to hydrogel state to release their loaded cargos by absorbing the body fluid in the dermis layer, and able to be withdrawn from the skin completely (without depositing needle tip materials in the skin) because of their insoluble network. Moreover, formation of the insoluble polymeric network through microcrystalline domains of PTM is achieved by a mild freeze-thaw treatment, for which bio-active agents may be loaded safely in the microneedle tips by adding in the polymer solution prior to molding without denaturing.

Abstract: The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules. The amino group-bearing monomers are those naturally existing or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine and spermidine (or their derivatives). Examples for the degradable chemical bonds formed between the amino group-bearing monomers are imines.

Abstract: A method of preparing polysaccharide glassy microparticles which are less than 10 ?um in diameter and contain structurally delicate agents, such as proteins, peptides, gene materials, vaccines, antibodies, viruses and liposomes using low-temperature aqueous-aqueous emulsification (free of polyelectrolytes) and freezing-induced phase separation. When delicate agents are added to a polysaccharide-PEG two phase system followed by homogenization (or other shear adding process), the agents partition into the polysaccharide dispersed phase preferentially. These processes help to avoid aggregation of proteins caused by interaction with charged polyelectrolytes used for stabilizing the polysaccharide dispersed phase in our previously reported aqueous-aqueous emulsion. When this system is frozen and lyophilized, glassy particles less than 10 ?m in diameter containing delicate agents can be formed.

Abstract: A new microsphere formulation (composition) for controlled- or sustained-release delivery of therapeutic ingredient(s), mainly peptides and proteins not over 10K in molecular weight, comprises at least a therapeutic ingredient, a helping agent (such as PH sensitive agent whose solubility is a function of pH) and a biodegradable polymer. The therapeutic ingredient(s) and the helping agent are in the form of fine particles, less than 1O um in diameter, encapsulated in the polymer which forms the microsphere matrix. A method for preparing the composition comprises a step of in-situ precipitating the therapeutic ingredient(s) and the helping agent to the fine particles and successive steps for forming the microspheres. Such a microsphere formulation offers a well-controlled release profile for prolonged period and encapsulation efficiency over 95%.

Abstract: A process for producing a small-sized, lipid-based cochleates. Cochleates are derived from liposomes which are suspended in an aqueous two-phase polymer solution, enabling the differential partitioning of polar molecule based-structures by phase separation. The liposome-containing two-phase polymer solution, treated with positively charged molecules such as Ca2+ or Zn2+, forms a cochleate precipitate of a particle size less than one micron. The process may be used to produce cochleates containing biologically relevant molecules.

Abstract: The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules. The amino group-bearing monomers are those naturally existing or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine and spermidine (or their derivatives). Examples for the degradable chemical bonds formed between the amino group-bearing monomers are imines.

Abstract: A process for producing a small-sized, lipid-based cochleates. Cochleates are derived from liposomes which are suspended in an aqueous two-phase polymer solution, enabling the differential partitioning of polar molecule based-structures by phase separation. The liposome-containing two-phase polymer solution, treated with positively charged molecules such as Ca2+ or Zn2+, forms a cochleate precipitate of a particle size less than one micron. The process may be used to produce cochleates containing biologically relevant molecules.

Abstract: This invention discloses a novel microneedle system, phase-transition microneedle patch, which overcomes all the limitations that existing microneedles encountered. The microneedle patch is formed of an integrated polymeric piece consisting of a microneedle array and a plate (called holding plate) on which the needles stand. The microneedles of the patch are hard and strong enough to penetrate epidermis at dry state but turn to be hydrogel state soft and permeable to hydrophilic agents when absorbing body fluid. The hydrogel state of the patch is a hydrophilic network held by physical or chemical cross-linking junctions. The pores of the network are opened up by body fluid for drugs and macromolecules to diffuse through. The polymeric materials used to form the microneedle patch have been used in the pharmaceutical field for years and have proven compatibility with the skin and with proteins.

Abstract: The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules or with themselves. The amino group-bearing monomers are those naturally existing in or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine, spermidine, serine or N,N-dimethyl serine, and histidine. Examples for the degradable chemical bonds formed between the amino group-bearing monomers are carbamate, imine, amide, carbonate, and ester.

Abstract: This invention provides a cochleate and nano-cochleate systems wherein the agents bridging lipid bilayer are organic multi-valent cations. This invention also provides a method for preparing the cochleate system comprising direct cochleation and hydrogel-isolated procedure. The preparation method comprises using the charge ration between the bridging agents and lipids to control the particle sizes. This cochleate or nano-cochleate system may be used for microencapsulation and delivery of therapeutics wherein the therapeutic agents are loaded in the cochleate structure as the bridging agents between lipid bilayers. Finally, this invention provides other uses of these new cochleate and nano- cochleate systems.