Butylphthalide oral solution and packaging material

Abstract

The invention discloses a butylphthalide oral solution and a packaging material, and relates to the technical field of pharmacy, the butylphthalide oral solution comprises butylphthalide, hydroxypropyl-beta-cyclodextrin and water for injection, and the mass ratio of butylphthalide to hydroxypropyl-beta-cyclodextrin to water is 1: 16.5-17.5: 35-65. According to the butylphthalide oral solution designed by the invention, the prescription proportion of hydroxypropyl-beta-cyclodextrin can be reduced, the clathration process is ensured, the safety is improved, and the product is effective and safe; the taste of the butylphthalide oral solution can be obviously improved by adding different auxiliary materials. And due to the specially-made packaging material, the contained oral solution has good stability and medicine effectiveness.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and particularly to a butylphthalide oral solution and a packaging material. Background Art

[0002] Butylphthalide, also known as apiumetin, can be extracted from celery seeds or synthesized artificially; butylphthalide is an oily liquid, insoluble in water and sensitive to light. Butylphthalide can reduce the infarct volume after focal cerebral ischemia, increase cerebral blood flow in the ischemic area and improve the microcirculation in the ischemic area of the brain, and reduce the degree of nerve function damage.

[0003] Cerebral ischemic diseases are extremely likely to cause symptoms such as coma, disturbance of consciousness, paralysis, limb numbness, etc. in patients, resulting in dysphagia or inability to eat orally. Therefore, traditional tablets, capsules or oral lyophilized powders are not very applicable; while injections are inconvenient to use and require a certain amount of time, and are not suitable for emergency treatment. For this reason, there is an urgent need for an easily swallowable butylphthalide oral preparation.

[0004] There are few reports on the oral preparations of butylphthalide in the prior art. The currently visible patent is a butylphthalide oral solution of CN116262102A, which uses hydroxypropyl betacyclodextrin as a cosolvent and a complexation promoter to increase the complexation rate.

[0005] In the prior art, a large amount of hydroxypropyl betacyclodextrin is used as a cosolvent for butylphthalide oral solution, which has a great impact on the absorption and metabolism of patients with cerebral ischemic diseases. Summary of the Invention

[0006] The technical solution of the present invention to solve the above technical problems is to provide a butylphthalide oral solution, which includes butylphthalide, hydroxypropyl betacyclodextrin and water for injection, wherein the mass ratio of butylphthalide, hydroxypropyl betacyclodextrin and water is 1:16.5 - 17.5:35 - 65.

[0007] Further, the butylphthalide oral solution further includes: a promoter, and the promoter is citric acid and / or sodium citrate.

[0008] Further, the butylphthalide oral solution further includes: excipients, and the excipients are sucralose, and / or sweet orange essence, and / or sodium chloride.

[0009] To solve the above technical problems, the present invention also provides a packaging material for containing the above-mentioned butylphthalide oral solution; the packaging material includes: a glass bottle, a rubber stopper and a gasket; wherein, the glass bottle is a sodium calcium glass controlled oral liquid bottle, and the rubber stopper and the gasket are easy-to-pierce chlorobutyl rubber stoppers and gaskets for oral preparations.

[0010] Compared with the prior art, the present invention has the following beneficial effects:

[0011] 1. This application reduces the formulation ratio of hydroxypropyl beta-cyclodextrin. While ensuring the inclusion process, it improves safety. The product is both effective and safe.

[0012] 2. Through stability tests, it is known that the combination of sodium calcium glass controlled oral liquid bottles and easy-pierce type chlorobutyl rubber stoppers and gaskets for oral preparations has no adsorption effect on butylphthalide. Through stability tests, it is proved that the easy-pierce type chlorobutyl rubber stoppers and gaskets for oral preparations and sodium calcium glass controlled oral liquid bottles are safe and effective as the packaging of butylphthalide oral solution. BRIEF DESCRIPTION OF THE DRAWINGS

[0013] In order to more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the following will briefly introduce the drawings required for use in the description of the embodiments or the prior art. Obviously, the following drawings are only some embodiments of the present invention. For those of ordinary skill in the art, without creative efforts, other drawings can be obtained based on the structures shown in these drawings.

[0014] Figure 1 It is the pharmacokinetic data trend chart of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0015] The present invention provides a butylphthalide oral solution and a packaging material, aiming to provide a butylphthalide oral solution with high concentration, small volume, simple preparation process, and less excipient addition.

[0016] The following will illustrate the butylphthalide oral solution proposed by the present invention in specific embodiments:

[0017] In the technical solution of this embodiment, a butylphthalide oral solution includes butylphthalide, hydroxypropyl beta-cyclodextrin, and injection water. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, and water is 1:16.5 - 17.5:35 - 65.

[0018] Furthermore, the butylphthalide oral solution further includes: a promoter, and the promoter is citric acid and / or sodium citrate.

[0019] Furthermore, the butylphthalide oral solution further includes: excipients, and the excipients are sucralose, and / or sweet orange essence, and / or sodium chloride.

[0020] Example 1:

[0021] A butylphthalide oral solution includes butylphthalide, hydroxypropyl beta-cyclodextrin, and injection water. Among them, the mass ratio of butylphthalide to hydroxypropyl beta-cyclodextrin is 1:16.5, and the specific prescription amount is 3 g of butylphthalide, 49.5 g of hydroxypropyl beta-cyclodextrin, and add injection water to make up to 150 ml.

[0022] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl betacyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0023] Example 2:

[0024] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl betacyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl betacyclodextrin is 1:17. The specific prescription amount is 3 g of butylphthalide, 51 g of hydroxypropyl betacyclodextrin, and add water for injection to make up the volume to 150 ml.

[0025] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl betacyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0026] Example 3:

[0027] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl betacyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl betacyclodextrin is 1:17.4. The specific prescription amount is 3 g of butylphthalide, 52.2 g of hydroxypropyl betacyclodextrin, and add water for injection to make up the volume to 150 ml.

[0028] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl betacyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0029] Example 4:

[0030] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl betacyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl betacyclodextrin is 1:17.5. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl betacyclodextrin, and add water for injection to make up the volume to 150 ml.

[0031] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl-β-cyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0032] Example 5:

[0033] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl-β-cyclodextrin is 1:17.5, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, and add water for injection to make up the volume to 180 ml.

[0034] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl-β-cyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0035] Example 6:

[0036] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl-β-cyclodextrin is 1:17.5, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, and add water for injection to make up the volume to 200 ml.

[0037] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl-β-cyclodextrin and add it to the water for injection. Start stirring at a stirring speed of 200 - 600 rpm. After stirring until completely dissolved, add the prescribed amount of butylphthalide and stir for 2 h - 6 h. After the solution is completely dissolved, cool it to room temperature, filter it through a 0.22 μm filter membrane and fill it; sterilize it at 121°C for 15 min.

[0038] Example 7:

[0039] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide to hydroxypropyl-β-cyclodextrin is 1:17.5, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, and add water for injection to make up the volume to 250 ml.

[0040] Preparation process: Weigh the prescribed amount of water for injection, heat the water temperature to 40°C - 60°C, weigh the prescribed amount of hydroxypropyl-β-cyclodextrin and add it to the water for injection, start stirring at a stirring speed of 200 - 600 rpm, stir until completely dissolved, then add the prescribed amount of butylphthalide, stir for 2 h - 6 h, cool the solution to room temperature after complete dissolution, filter through a 0.22 μm filter membrane and fill; sterilize at 121°C for 15 min.

[0041] Example 8:

[0042] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl-β-cyclodextrin, and sweet orange essence is 1:17.5:0.025, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, 0.075 g of sweet orange essence, and add water for injection to make up to 150 ml.

[0043] Example 9:

[0044] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl-β-cyclodextrin, and sodium chloride is 1:17.5:0.45, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, 1.35 g of sodium chloride, and add water for injection to make up to 150 ml.

[0045] Example 10:

[0046] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl-β-cyclodextrin, and citric acid is 1:17.5:0.09, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, 0.27 g of citric acid, and add water for injection to make up to 150 ml.

[0047] Example 11:

[0048] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl-β-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl-β-cyclodextrin, and sodium citrate is 1:17.5:0.09, and the specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl-β-cyclodextrin, 0.27 g of sodium citrate, and add water for injection to make up to 150 ml.

[0049] Example 12:

[0050] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin and sucralose is 1:17.5:0.0125. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.0375 g of sucralose, and water for injection is added to make the volume up to 150 ml.

[0051] Example 13:

[0052] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride and citric acid is 1:17.5:0.45:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.27 g of citric acid, and water for injection is added to make the volume up to 150 ml.

[0053] Example 14:

[0054] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride and sodium citrate is 1:17.5:0.45:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.27 g of sodium citrate, and water for injection is added to make the volume up to 150 ml.

[0055] Example 15:

[0056] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride, sweet orange essence is 1:17.5:0.45:0.025:0.0125. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.075 g of sweet orange essence, and water for injection is added to make the volume up to 150 ml.

[0057] Example 16:

[0058] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium citrate, sweet orange essence is 1:17.5:0.09:0.025. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.27 g of sodium citrate, 0.075 g of sweet orange essence, and water for injection is added to make the volume up to 150 ml.

[0059] Example 17:

[0060] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, citric acid, and sweet orange essence is 1:17.5:0.09:0.025. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.27 g of citric acid, 0.075 g of sweet orange essence, and water for injection is added to make the volume up to 150 ml.

[0061] Example 18:

[0062] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium citrate, and sweet orange essence is 1:17.5:0.09:0.025. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.27 g of sodium citrate, 0.075 g of sweet orange essence, and water for injection is added to make the volume up to 150 ml.

[0063] Example 19:

[0064] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sucralose, and sodium citrate is 1:17.5:0.0125:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.27 g of sodium citrate, 0.0375 g of sucralose, and water for injection is added to make the volume up to 150 ml.

[0065] Example 20:

[0066] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sucralose, and citric acid is 1:17.5:0.0125:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.27 g of citric acid, 0.0375 g of sucralose, and water for injection is added to make the volume up to 150 ml.

[0067] Example 21:

[0068] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride, citric acid, and sodium citrate is 1:17.5:0.45:0.09:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.27 g of citric acid, 0.27 g of sodium citrate, and water for injection is added to make the volume up to 150 ml.

[0069] Example 22:

[0070] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sucralose, citric acid and sodium citrate is 1:17.5:0.0125:0.09:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.0375 g of sucralose, 0.27 g of citric acid, 0.27 g of sodium citrate, and add water for injection to make up the volume to 150 ml.

[0071] Example 23:

[0072] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, orange essence, citric acid and sodium citrate is 1:17.5:0.025:0.09:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.075 g of orange essence, 0.27 g of citric acid, 0.27 g of sodium citrate, and add water for injection to make up the volume to 150 ml.

[0073] Example 24:

[0074] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, orange essence and sucralose is 1:17:0.025:0.0125. The specific prescription amount is 3 g of butylphthalide, 51 g of hydroxypropyl beta-cyclodextrin, 0.075 g of orange essence, 0.0375 g of sucralose, and add water for injection to make up the volume to 150 ml.

[0075] Example 25:

[0076] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, orange essence and sucralose is 1:17.5:0.025:0.09:0.09. The specific prescription amount is 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.075 g of orange essence, 0.0375 g of sucralose, and add water for injection to make up the volume to 150 ml.

[0077] Example 26:

[0078] A butylphthalide oral solution, comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, orange essence and sucralose is 1:16.5:0.025:0.0125. The specific prescription amount is 3 g of butylphthalide, 49.5 g of hydroxypropyl beta-cyclodextrin, 0.075 g of orange essence, 0.0375 g of sucralose, and add water for injection to make up the volume to 150 ml.

[0079] Example 27:

[0080] A butylphthalide oral solution comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride, sodium citrate, and sucralose is 1:17.5:0.45:0.09:0.0125. The specific prescription amounts are 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.27 g of sodium citrate, 0.0375 g of sucralose, and add water for injection to make up to 150 ml.

[0081] Example 28:

[0082] A butylphthalide oral solution comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride, sweet orange essence, and sucralose is 1:17.5:0.45:0.025:0.0125. The specific prescription amounts are 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.075 g of sweet orange essence, 0.0375 g of sucralose, and add water for injection to make up to 150 ml.

[0083] Example 29:

[0084] A butylphthalide oral solution comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sweet orange essence, sucralose, sodium citrate, and citric acid is 1:17.5:0.025:0.0125:0.09:0.09. The specific prescription amounts are 3 g of butylphthalide, 52.5 g of hydroxypropyl beta-cyclodextrin, 0.075 g of sweet orange essence, 0.0375 g of sucralose, 0.27 g of sodium citrate, 0.27 g of citric acid, and add water for injection to make up to 150 ml.

[0085] Example 30:

[0086] A butylphthalide oral solution comprising butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection. Among them, the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin, sodium chloride, sucralose, sodium citrate, citric acid, and sweet orange essence is 1:17.4:0.45:0.0125:0.09:0.09:0.0125. The specific prescription amounts are 3 g of butylphthalide, 52.2 g of hydroxypropyl beta-cyclodextrin, 1.35 g of sodium chloride, 0.0375 g of sucralose, 0.27 g of sodium citrate, 0.27 g of citric acid, 0.0375 g of sweet orange essence, and add water for injection to make up to 150 ml.

[0087] Example 31:

[0088] A packaging material for containing the above-mentioned butylphthalide oral solution; the packaging material includes: a glass bottle, a rubber stopper, and a gasket. Among them, the glass bottle is a sodium-calcium glass controlled oral liquid bottle, and the rubber stopper and gasket are easy-to-puncture chlorobutyl rubber stoppers and gaskets for oral preparations. The material of the glass bottle is sodium-calcium glass, and the materials of the rubber stopper and gasket are easy-to-puncture chlorobutyl rubber.

[0089] Taste test:

[0090] 1. Test method

[0091] Take the above samples for manual tasting and score according to the degree of pungency and irritation in the throat. The score is from 0 to 10: no pungency or almost no pungency in the throat is 8 - 10 points, strong pungency or unbearable pungency in the throat is 0 - 4 points, and the taste between the two is scored 5 - 7 points according to personal feelings. Finally, calculate the average score of each sample. A score between 8 - 10 points is finally evaluated as grade A, 5 - 7 points as grade B, and 0 - 4 points as grade C.

[0092] 2. Test results

[0093] Sample Example 1 Example 2 Example 3 Example 4 Example 5 Example 6 Taste C C C C C C Sample Example 7 Example 8 Example 9 Example 10 Example 11 Example 12 Taste C A A A A A Sample Example 13 Example 14 Example 15 Example 16 Example 17 Example 18 Taste A A A A A A Sample Example 19 Example 20 Example 21 Example 22 Example 23 Example 24 Taste A A A A A A Sample Example 25 Example 26 Example 27 Example 28 Example 29 Example 30 Taste A A A A A A

[0094] The above table shows that although hydroxypropyl beta-cyclodextrin has a very strong solubilizing effect on butylphthalide, it cannot mask the taste of butylphthalide and has a strong pungency and irritation in the throat. When citric acid, sodium citrate, essence, and sucralose are added to the prescription, the taste of the butylphthalide oral solution can be significantly improved. There will be a slightly sweet aftertaste after this oral solution enters the throat.

[0095] Stability test:

[0096] 1. Test method

[0097] Use the sodium-calcium glass controlled oral liquid bottle and the easy-to-puncture chlorobutyl rubber stopper and gasket for oral preparations disclosed in Example 31 to package the samples and place them under light conditions for 30 days to investigate the stability in the upright and inverted positions.

[0098] 2. Test results

[0099]

[0100]

[0101]

[0102] The above table shows that the stability of each prescription with the specific packaging materials (sodium-calcium glass controlled oral liquid bottle and easy-to-puncture chlorobutyl rubber stopper and gasket for oral preparations) is good.

[0103] Animal test:

[0104] 1. Test method

[0105] 1) Experimental animals

[0106] Rats (SD, 250 g ± 30 g), 3 rats, male, 1 control group (male).

[0107] 2) Drug administration plan

[0108] One day before the experiment, after fasting the rats for 8 h - 12 h, a single dose of butylphthalide oral solution (18 mg / kg) was intragastrically administered on an empty stomach early the next morning. After 2 h, they were allowed to drink water freely, and after 4 h, they were fed uniformly.

[0109] 3) Blood sample collection

[0110] Blood was collected from the tail vein at 5 min, 15 min, 30 min, 1 h, 1.5 h, 2 h, 3 h, 4 h, 6 h, 8 h, 12 h, 24 h, 36 h, 48 h, 60 h, and 72 h after administration, with at least 200 μL.

[0111] 4) Sample pretreatment

[0112] 200 μL of different blood samples was aspirated into a centrifuge tube, 500 μL of methanol was precisely added, vortexed for 1 min, and then centrifuged for 3 min. The supernatant was taken and filtered through a 0.22 μm filter membrane for liquid chromatography - tandem mass spectrometry determination.

[0113] 2. Test results

[0114] The pharmacokinetic data are shown in the following table, and the data trend chart is shown in the following table:

[0115]

[0116] As Figure 1 shown, the drug shows linear absorption and distribution in rats. The blood concentration can reach the peak in about 15 minutes, and the drug concentration can last for 8 hours in rats, proving the effectiveness of the drug.

[0117] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by those skilled in the art within the technical scope disclosed by the present invention should be covered by the protection scope of the present invention. Therefore, the protection scope of the present invention should be subject to the protection scope of the claims.

Claims

1. A butylphthalide oral solution, characterized in that: The invention comprises butylphthalide, hydroxypropyl beta-cyclodextrin and water for injection, wherein the mass ratio of butylphthalide, hydroxypropyl beta-cyclodextrin and water is 1:16.5-17.5:35-65.

2. The butylphthalide oral solution according to claim 1, characterized in that Also includes: The accelerator is citric acid and / or sodium citrate.

3. The butylphthalide oral solution according to claim 1 or 2, characterized in that Also includes: Auxiliary materials, the auxiliary materials are sucralose, and / or sweet orange flavor, and / or sodium chloride.

4. A packaging material for containing the butylphthalide oral solution according to claim 1; characterized in that: Packaging materials include: glass bottles, rubber stoppers and gaskets; Among them, the glass bottle is a soda-lime glass tube oral liquid bottle, and the rubber stopper and gasket are puncture-resistant chlorobutyl rubber stoppers and gaskets for oral preparations.

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