Sustained-release drug delivery system

[0102] Example 1 Solution of different types of saturated phospholipids in castor oil and each organic solvent

[0103]1g castor oil, organic solvent was added to the EP tube, and 0.1 g of saturated phospholipids (about 100 mg / g, 10% w / w), 50 ° C ultrasound, observed dissolution, and the results are shown in Table 1-1.

[0104] Table 1-1 Investigation of solubility

[0105]

[0106] Among them, ETOH represents anhydrous ethanol; BB represents benzyl benzoate; BA represents benzyl alcohol; NMP represents N-methylpyrrolidone; DMSO represents dimethyl sulfoxide.

[0107] According to the dissolution, saturated phospholipid (HSPC, DPPC, DMPC, DSPC) has better solubility in alcohol solvents (ethanol, benzyl alcohol, propylene glycol, etc.), and phosphatidylglycerol (DPPG), phosphatidyl ethanolamine (DPPE) However, phosphatidic acid (DPPA) category cannot be solved in the above solvent.

[0108] Example 2 Combination ratio studies

[0109] (1) Combination room temperature morphology test

[0110] The composition is prepared according to each of the ingredients and ingredients shown in Table 2-1 below. The solvent phospholipin, oil and solvent are mixed, and the mixture is stirred while heating the heating edge until a solution of a transparent uniform, cooling to room temperature, and investigating the physical form. At the same time, the room temperature morphology of unsaturated phospholipid composition is carried out as a comparative study.

[0111] Table 2-1 Room Temperature of Compositions under Different Metals

[0112]

[0113] This example examines a form of formulation containing 0.5 to 30% (W / W) saturated phospholipids (HSPC, DPPC, DSPC and DMPC), 0 to 50% (w / w) solvent, and the results are shown in Table 2 According to the composition of the composition room temperature of the present invention, the composition of the present invention is related to the amount of saturated phospholipid and solvent, and can be used to form a semi-solid or liquid preparation, which can be used for different routes of administration.

[0114] In this embodiment, the unsaturated phospholipid composition is compared, and the composition of the composition containing unsaturated phospholipids (SPC and EPC) is a solution form, and a semi-solid preparation is not obtained.

[0115] (2) Study on the formation of differentiated liquid compositions to add water

[0116] A liquid composition containing 0.5 to 30% saturated phospholipids, 10 ~ 45% solvent is prepared according to Table 2-2, and a liquid composition of 3 to 5% gel factor or 10 to 30% release modifier, phospholipids and solvents Mix until the solution was mixed, and the castor oil was added to the mixed solution until completely mixed uniform, and the liquid composition containing unsaturated phospholipid was prepared as a contrast. 0.5 mL of the composition was taken into an overvoltage, and the morphological changes of the compositions in 2 hours after water were investigated.

[0117] Table 2-2 Different comparison liquid compositions are added to the water

[0118]

[0119] Note: The "phospholipid" component in each group corresponds to HSPC, DPPC, DMPC, SPC, EPC, for example, the phospholipid of the HSPC group is HSPC; "SPC" components in each group are released as a release modifier, for example Among the DPPC group, the phospholipid was DPPC and SPC was released regulatory agents.

[0120] The results showed that the liquid composition containing saturated phosphipid (HSPC, DPPC and DMPC) can be rapidly rubberized, but only 10% or 30% of unsaturated phospholipids (SPC and EPC) could not be in 2 hours. Elastic.

[0121] Example 3

[0122] (1) Effect of different types of phospholipids on the phase change of the composition

[0123] A pharmaceutical composition containing saturated phospholipid (composition 16), no phospholipid (pure castor oil group) and an unsaturated phospholipid is prepared according to Table 3-1. The methalkoxin is dissolved in N-methylpyrrolidone, and the concentrated solution of 50 mg / g is prepared, and ropivacaine, soybean phospholipid or dioplamyyl phosphatidine choline is added to liquid oil, solvent and machetin at 50 ° C. In the heating solution, the mixture is stirred while heating the heating edge until a solution of a transparent uniform is cooled to room temperature. The composition was slowly injected into water with a syringe to observe the morphological changes in the water in the water. See Picture 1-1.

[0124] Table 3-1 Different compositions

[0125]

[0126] The above experiments respectively examined the morphological changes of a composition (unsaturated phospholipid group) containing saturated phospholipids and containing soy-containing phospholipids, as well as the phospholipid-containing composition (pure castor oil group) in water. Picture 1-1. The composition containing unsaturated phospholipids and composition without phospholipid is added to the surface after the droplet form, and the composition containing the same ratio (10% by weight) is formed, and the reservoir is formed immediately after contact with water. Substance. Further explanation of saturated phospholipids is a key factor in the transformation of the compositions of the present invention.

[0127] (2) Comparative test of unsaturated phospholipids

[0128] The composition containing the same ratio of different phospholipids (HSPC, SPC, EPC) is prepared according to Table 3-2, and the phase transition results of each prescription are added to the water. picture 2-1. After standing for 30 minutes, slowly shake, observe changes in the formulation, see Figure 2-2.

[0129] Table 3-2 Composition of unsaturated phospholipids

[0130]

[0131] by picture 2-1 It can be seen that the HSPC group can be quickly phase change after adding water, and it is translucent to white; and the SPC group and the EPC group are floated after the surface, and there is no obvious phase transition. Figure 2-2 In order to stand 30 min, the changes of each prescription, the HSPC group change is complete, and a better reservoir can be formed. After the shake, the aqueous solution is still a clear state, the SPC group and the EPC resolution have turbid, and it is impossible to form a desirable. Reservoir form.

[0132] Compositions containing high concentration of unsaturated phospholipids (SPC) were prepared according to Table 3-3, and the combined articles were added dropwise to excess water to observe changes in the aqueous solution. Next, aqueous solution is added dropwise to the composition, shake mixing, and observe changes in the composition. See Figure 2-3 In the high concentration SPC composition, the water drop is added to the high concentration SPC composition, and the viscosity is increased, but the invert will flow slowly (left on the left). The high concentration SPC composition was added to an overvoltage, which may be formed, but the vibrating solution changed to turbid (on the right side).

[0133] Table 3-3 High concentration unsaturated phospholipid (SPC) composition

[0134]