CN-121987556-A - In-situ gel preparation and preparation method thereof

Abstract

In some embodiments of the present disclosure, an in situ gel formulation is provided comprising an active ingredient, a solvent, a polymer, and a lipid, wherein the polymer comprises poly (lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), or a combination thereof, and the lipid comprises a fatty acid, a fatty alcohol, a glyceride, a phospholipid, or a combination thereof. In some embodiments of the present disclosure, methods of preparing in situ gel formulations are also provided. By adding lipids to the polymer-containing formulation, the polymer content is reduced, thereby reducing viscosity and reducing inflammation while maintaining a long-lasting sustained release effect and overcoming the limitations of low temperature storage.

Inventors

• LI XIANGRU
• SU JIAYU
• CHEN MEIHUI
• LIU YIXIANG
• Zhan Huajing
• JIAN QIHENG

Assignees

• 莹硕生技医药股份有限公司

Dates

Publication Date

20260508

Application Date

20251103

Priority Date

20241104

Claims (20)

1. 1. An in situ gel formulation comprising: An active ingredient; A solvent; a polymer, wherein the polymer comprises poly (lactic-co-glycolic acid), polylactic acid, or a combination thereof, and A lipid, wherein the lipid comprises a fatty acid, a fatty alcohol, a glyceride, a phospholipid, or a combination thereof.
2. 2. The in situ gel formulation of claim 1, wherein the weight percent of the active ingredient is from 0.1% to 35% when the weight percent of the in situ gel formulation is taken as 100%.
3. 3. The in situ gel formulation of claim 1, wherein the active ingredient comprises a psychotropic drug or a diabetic drug.
4. 4. The in situ gel formulation of claim 3, wherein the psychotropic drug comprises a calicheazine, a bripiprazole, a paliperidone, a risperidone, an aripiprazole, a lurasidone, a pharmaceutically acceptable salt of any of the foregoing psychotropic drugs, or a combination thereof.
5. 5. The in situ gel formulation of claim 3, wherein the diabetes drug comprises engagliflozin, dapagliflozin, canagliflozin, cord Ma Lutai, liraglutide, dolraglutide, telpofungin, a pharmaceutically acceptable salt of any of the foregoing, or a combination thereof.
6. 6. The in situ gel formulation of claim 1, wherein the weight percent of the polymer is from 2.5% to 20% when the weight percent of the in situ gel formulation is taken as 100%.
7. 7. The in situ gel formulation of claim 1, wherein the molar ratio of lactic acid to glycolic acid in the poly (lactic-co-glycolic acid) is 50:50 to 99:1.
8. 8. The in situ gel formulation of claim 1, wherein the weight percent of the lipid is 17.5% to 60% when the weight percent of the in situ gel formulation is taken as 100%.
9. 9. The in situ gel formulation of claim 1, wherein the weight percent of the lipid is from 55% to 95% when the total weight percent of the polymer and the lipid is taken as 100%.
10. 10. The in situ gel formulation of claim 1, wherein the weight percent of the polymer and the lipid is 25% to 65% when the weight percent of the in situ gel formulation is 100%.
11. 11. The in situ gel formulation of claim 1, wherein the solvent comprises ethanol, dimethyl sulfoxide, N-methyl-2-pyrrolidone, or a combination thereof.
12. 12. The in situ gel formulation of claim 1, further comprising a surfactant.
13. 13. The in situ gel formulation of claim 12, wherein the surfactant has a hydrophilic-lipophilic balance of from 15 to 20.
14. 14. The in situ gel formulation of claim 13, wherein the hydrophilic-lipophilic balance of the surfactant is from 16 to 18.
15. 15. The in situ gel formulation of claim 12, wherein the weight percent of the surfactant is from 2.5% to 10% when the weight percent of the in situ gel formulation is taken as 100%.
16. 16. A method for preparing an in situ gel formulation, comprising: Mixing an active ingredient, a polymer, and a first solvent to form a first mixture; Mixing the lipid with a second solvent to form a second mixture, and Mixing the first mixture and the second mixture to form an in situ gel formulation.
17. 17. The method of claim 16, wherein mixing the active ingredient, the polymer, and the first solvent comprises: mixing the active ingredient with the first solvent to form a premix, and Mixing the premix and the polymer to form the first mixture.
18. 18. The method of claim 16, wherein mixing the lipid and the second solvent comprises mixing the lipid, the second solvent, and a surfactant.
19. 19. A method for preparing an in situ gel formulation, comprising: Mixing a polymer with a solvent to form a polymer mixture; Mixing the active ingredients with a lipid to form a lipid mixture, and Mixing the polymer mixture and the lipid mixture to form an in situ gel formulation.
20. 20. The method of claim 19, wherein mixing the polymer and the solvent comprises mixing the polymer, the solvent, and a surfactant.

Description

In-situ gel preparation and preparation method thereof Technical Field The present disclosure relates to in situ gel formulations and methods of making the same. In particular, the present disclosure relates to in situ gel formulations comprising a polymer and a lipid. Background An in situ gel formulation is a gel implant formulation with sustained release properties, typically requiring high levels of polymer. However, high levels of polymer suffer from certain disadvantages such as the use of large needles due to excessive viscosity, increased storage and transportation costs due to the need for low temperature storage to maintain quality, and inflammatory reactions caused by polymer degradation byproducts. Thus, it is an object to provide an in situ gel formulation that ameliorates the foregoing problems. Disclosure of Invention In one aspect of the present disclosure, an in situ gel formulation is provided that includes an active ingredient, a solvent, a polymer, and a lipid, wherein the polymer includes poly (lactic-co-glycolic acid) (PLGA), polylactic acid (PLA), or a combination thereof, and the lipid includes a fatty acid (FATTY ACID), a fatty alcohol (fat alcohol), a glyceride (glyceride), a phospholipid (phospholipid), or a combination thereof. In some embodiments, the weight percent of active ingredient is 0.1% to 35% when the weight percent of the in situ gel formulation is 100%. In some embodiments, the active ingredient comprises a psychotropic drug (PSYCHIATRIC DRUG) or a diabetes drug (antidiabetic drug). In some embodiments, the psychotropic drug comprises cariprazine (cariprazine), bripiprazole (brexpiprazole), paliperidone (paliperidone), risperidone (risperidone), aripiprazole (aripiprazole), lurasidone (lurasidone), a pharmaceutically acceptable salt of any of the foregoing psychotropic drugs, or a combination thereof. In some embodiments, the diabetic drug comprises engagliflozin (empagliflozin), dapagliflozin (dapagliflozin), canagliflozin (canagliflozin), solitary Ma Lutai (semaglutide), liraglutide (liraglutide), dolraglutide (dulaglutide), telipopeptide (tirzepatide), a pharmaceutically acceptable salt of any of the foregoing, or a combination thereof. In some embodiments, the weight percent of the polymer is 2.5% to 20% when the weight percent of the in situ gel formulation is 100%. In some embodiments, the molar ratio of lactic acid (LACTIC ACID) to glycolic acid (glycolic acid) in poly (lactic-co-glycolic acid) (PLGA) is 50:50 to 99:1. In some embodiments, the weight percent of lipid is 17.5% to 60% when the weight percent of the in situ gel formulation is 100%. In some embodiments, the weight percent of lipid is 55% to 95% when the total weight percent of polymer and lipid is taken as 100%. In some embodiments, the weight percent of polymer and lipid is 25% to 65% when the weight percent of the in situ gel formulation is 100%. In some embodiments, the solvent comprises ethanol (EtOH), dimethyl sulfoxide (dimethyl sulfoxide, DMSO), N-Methyl-2-pyrrolidone (1-Methyl-2-pyrrolidone, NMP), or a combination thereof. In some embodiments, the in situ gel formulation further comprises a surfactant. In some embodiments, the surfactant has a hydrophile-lipophile balance (HLB value) of 15 to 20. In some embodiments, the surfactant has a hydrophilic-lipophilic balance of from 16 to 18. In some embodiments, the weight percent of surfactant is 2.5% to 10% when the weight percent of the in situ gel formulation is 100%. In one aspect of the present disclosure, a method of preparing an in situ gel formulation is provided that includes mixing an active ingredient, a polymer, and a first solvent to form a first mixture, mixing a lipid and a second solvent to form a second mixture, and mixing the first mixture and the second mixture to form an in situ gel formulation. In some embodiments, mixing the active ingredient, the polymer, and the first solvent includes mixing the active ingredient and the first solvent to form a premix, and mixing the premix and the polymer to form a first mixture. In some embodiments, mixing the lipid with the second solvent includes mixing the lipid, the second solvent, and the surfactant. In one aspect of the present disclosure, a method of preparing an in situ gel formulation is provided that includes mixing a polymer and a solvent to form a polymer mixture, mixing an active ingredient and a lipid to form a lipid mixture, and mixing the polymer mixture and the lipid mixture to form an in situ gel formulation. In some embodiments, mixing the polymer with the solvent includes mixing the polymer, the solvent, and the surfactant. Drawings The foregoing and other objects, features, advantages and embodiments of the present disclosure will be more fully understood from the following detailed description of the embodiments taken in conjunction with the accompanying drawings. Fig. 1A illustrates a flow chart of a method of preparing an in situ gel formulation in some embodimen