阅读说明：本技术 包含聚(噁唑啉)稳定剂的有机聚合物颗粒以及聚(噁唑啉)用于稳定有机聚合物颗粒的用途 (Organic polymer particles comprising poly (oxazoline) stabilizers and use of poly (oxazoline) for stabilizing organic polymer particles ) 是由 M·N·莱斯克 A·特拉格 U·S·舒伯特 于 2018-03-12 设计创作，主要内容包括：描述了组合物,所述组合物包含可溶于水的聚(噁唑啉)和选自下组的有机聚合物颗粒：聚烯烃、聚乙烯基芳香族化合物、聚乙烯基酯、聚酯、聚酰胺、聚酰亚胺、聚羧酸、聚羧酸酯、聚羧酸酰胺、聚腈、聚磺酸、聚酮、聚砜、聚合物型多元醇、聚氨酯、蛋白质、聚合物型碳水化合物、核酸或者这些聚合物中两种或更多种的混合物。所述可溶于水的聚(噁唑啉)作为聚合物颗粒的稳定剂起作用并且能够特别有利地在冻干水性聚合物分散体时作为稳定剂使用。(Described are compositions comprising a water-soluble poly (oxazoline) and organic polymer particles selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers. The water-soluble poly (oxazoline) acts as a stabilizer for the polymer particles and can be used particularly advantageously as a stabilizer when lyophilizing aqueous polymer dispersions.)

1. A composition comprising a water-soluble poly (oxazoline) and organic polymer particles selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers.

2. The composition as claimed in claim 1, wherein the organic polymer particles have an average diameter D50 of less than 10 μm.

3. Composition according to claim 2, characterized in that the organic polymer particles have an average diameter D50 of less than 1 μm.

4. Composition according to at least one of claims 1 to 3, characterized in that the organic polymer particles have a diameter in the range of 50 to 999 nm.

5. Composition according to at least one of claims 1 to 4, characterized in that the organic polymer particles form a dispersed phase in a hydrophilic liquid.

6. The composition of claim 5, wherein the organic polymer particles are suspended in a hydrophilic liquid.

7. Composition according to at least one of claims 1 to 6, characterized in that the organic polymer particles are present in solid form or are coated with poly (oxazoline).

8. Composition according to at least one of claims 1 to 7, characterized in that the organic polymer particles comprise a polyester.

9. The composition of claim 8, wherein the polyester is a polyhydroxyalkanoate.

10. The composition of claim 9, wherein the polyhydroxyalkanoate is a lactic acid homopolymer or a lactic acid copolymer.

11. Composition according to at least one of claims 1 to 10, characterized in that the water-soluble poly (oxazoline) has at least 80% by weight, relative to its total mass, of recurring structural units of formula I and/or of formula II

-NR-CRH-CRH-(I)，-NR-CRH-CRH-CRH-(II)，

Wherein

R1 represents a residue of formula-CO-R2,

R3, R4 and R5 independently of one another denote hydrogen, methyl, ethyl, propyl or butyl,

R2 is selected from the group consisting of hydrogen, methyl, ethyl, -CmH2m-X or- (CnH2n-O) O- (CpH2p-O) q-R6,

R6 is hydrogen or C1-C6 alkyl,

m is an integer of 1 to 6,

X is selected from the group consisting of hydroxy, alkoxy, amino, N-alkylamino, N-dialkylamino, carboxy, carboxylate, sulfonyl, sulfonate or carbamate,

n and p are independently of each other an integer from 2 to 4, where n is not equal to p, and

o and q are independently integers from 0 to 60, wherein at least one of o or q is not equal to 0.

12. The composition according to claim 11, characterized in that R2 is hydrogen, methyl or ethyl and R3 to R5 represent hydrogen, or wherein R2 is hydrogen, methyl or ethyl and two of the residues R3 to R5 are hydrogen and one of the residues R3 to R5 is methyl or ethyl.

13. Composition according to at least one of claims 11 or 12, characterized in that the water-soluble poly (oxazoline) has at least 90% by weight, relative to its total mass, of recurring structural units of formula I, in which R2 represents a methyl or ethyl group.

14. composition according to at least one of the claims 1 to 13, characterized in that the organic polymer particles comprise one or more pharmaceutically effective substances.

15. Use of a water-soluble poly (oxazoline) for stabilizing organic polymer particles selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers.

16. Use of a water-soluble poly (oxazoline) for stabilizing organic polymer particles selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers.

17. Use of a water-soluble poly (oxazoline) as a stabiliser in a hydrophilic liquid in the preparation or treatment of organic polymer particles selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers.

18. Use of a water-soluble poly (oxazoline) for stabilizing organic polymer particles in powder form selected from the group consisting of: polyolefins, polyvinylaromatics, polyvinylesters, polyesters, polyamides, polyimides, polycarboxylic acids, polycarboxylates amides, polynitriles, polysulfonic acids, polyketones, polysulfones, polymeric polyols, polyurethanes, proteins, polymeric carbohydrates, nucleic acids or mixtures of two or more of these polymers.

Example 1: preparation of Poly (2-oxazoline) (POx)

The synthesis of poly (2-oxazoline) has been described in the literature (see, e.g., Wiesbrock, F.et al. macromolecular Rapid Communications 2004,25, 1895-1899). Thus, the process is exemplarily described for poly (2-ethyl-2-oxazoline) (p (etox)61) having a Degree of Polymerization (DP) of 61.

2-ethyl-2-oxazoline (6.06mL, 60.0mmol), methyl tosylate (0.15mL, 0.1mmol) and acetonitrile (8.79mL) were combined under inert conditions in a microwave reaction vessel. The reaction vessel was then heated in a synthesis microwave for 14 minutes to 140 ℃. The reaction was then quenched by addition of 0.5mL of deionized water and stirred at room temperature overnight. The resulting solution was purified by diluting it with dichloromethane and then precipitating in excess ice-cold diethyl ether. The precipitated polymer was then filtered and dissolved in dichloromethane. The solvent is subsequently removed on a rotary evaporator and the polymer is dried under high vacuum until completely free of solvent. The final product exists as a crystalline white solid. 1H-NMR (CDCl3, 300 MHz). delta. delta.4.34 (0.1H, s, backbone-OH), 3.44(4.0H, s, backbone), 3.02(0.3H, s, CH 3-backbone), 2.4(1.7H, m, CH2(EtOx)),1.11(2.5H, s, CH3(EtOx)) ppm.

SEC (eluent: DMAc1), 0.21% LiCl, PS2) standard) Mn 11.200g mol-1, Mw 12.200g mol-1, D1.09.

FIG. 1 shows the 1H-NMR (300MHz, CDCl3,) profile of P (EtOx) 61.

Figure 2 shows a volume exclusion chromatogram of p (etox)61 (DMAc1), 0.21% LiCl, PS2) calibration).

1) DMAc ═ dimethylacetamide

2) PS ═ polystyrene