Other

Biopharm Solutions Inc.

Shanghai Jiao Tong University

Blodvery Pharmatech, Ltd

Jin, Tuo

Tuo Jin

Fei Wu

Weien Yuan

Hua Zhu

Raphael J Mannino

Zhenhua Hu

Li Chen

Jiahao Zhu

Leila Zarif

Ignacio Segarra

Shiyue Duan

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.

Method to print microneedle patches rapidly

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.

Process for producing polymeric microspheres

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.

Fabrication process of phase-transition microneedle patch

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%.

Microspheres for controlled- or sustained-release delivery of therapeutics

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.

Phase-transition polymeric microneedles

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. In order to improve degradability or proton sponging effect, low pKa (&#x3c;8) amino group(s), free amino groups generated by polymer degradation (such as those generated by degradation of imine linkages), or other electron donating group(s) such as imidazole, pyrazole, pyridine, pyrimidine, or even benzene is incorporated in the linker between the two (or three) reactive groups for linking the amino group-bearing monomers. These polycationic carrier systems can be used for nano-encapsulation and transfection of gene materials.

Cationic polymers formed from amino group-bearing monomers and heterocyclic linkers

A method of preparing polysaccharide glassy microparticles which are less than 10 &#x3bc;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 &#x3bc;m in diameter containing delicate agents can be formed. These fine polysaccharide particles protect proteins within their hydrophilic glassy matrix, and can therefore be easily suspended in hydrophobic polymer solutions and formulated to various forms of sustained release devices such microsphere, sheets, fibers, coating layers, and scaffolds. The particles can also be dispersed in hydrophilic gels to improve releasing kinetics and to deliver vaccines and antibodies for immune therapy.

Polysaccharide microparticles containing biological agents: their preparation and applications

This invention provides method for sustained release delivery of structurally delicate agents such as proteins and peptides. Using a unique emulsion system (Stable polymer aqueous-aqueous emulsion), proteins and peptides can be microencapsulated in polysacchride glassy particles under a condition free of any chemical or physical hazard such as organic solvents, strong interfacial tension, strong shears, elevated temperature, large amount of surfactants, and cross-linking agents. Proteins loaded in these glassy particles showed strong resistance to organic solvents, prolonged activity in hydrated state, and an excellent sustained release profile with minimal burst and incomplete release when being further loaded in degradable polymer microspheres. This invention provides a simple yet effective approach to address all the technical challenges raised in sustained release delivery of proteins.

Aquespheres, their preparation and uses thereof

This invention provides a stable aqueous/aqueous emulsion system which is prepared with a hydrophilic polymer. This invention also provides the method of preparing a stable aqueous/aqueous emulsion. Finally, this invention provides an encapsulation comprising the emulsion system which is prepared with a hydrophilic polymer.

Stable polymer aqueous/aqueous emulsion system and uses thereof

A process for producing a small-sized, lipid-based cochleate. 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 Ca or Zn , forms a cochleate precipitate of a particle size less than one micron. The process may be used to produce cochleates containing biologically relevant molecules.

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Shanghai, China

Tuo Jin