Eyesight-improving pearl eye drops and preparation method thereof

Abstract

The invention relates to pearl eyesight-improving eye drops and a preparation method thereof.The pearl eyesight-improving eye drops are composed of pearl liquid, borneol, sodium glycerophosphate, poloxamer 188, ethyl alcohol and water for injection and can further contain sodium chloride and ethylparaben, the poloxamer 188, the sodium glycerophosphate and the ethyl alcohol serve as auxiliary materials of the pearl eyesight-improving eye drops, and the two auxiliary materials of the poloxamer 188 and the sodium glycerophosphate are used, so that the eyesight-improving effect of the pearl eyesight-improving eye drops is improved. According to the preparation method, the dosage of ethanol can be greatly reduced under the condition that borneol in the pearl eyesight-improving eye drops is completely dissolved, and in addition, the stability of the obtained pearl eyesight-improving eye drops is also remarkably improved.

Description

Technical Field

[0001] The invention belongs to the technical field of medicine, and particularly relates to pearl eyesight-improving eye drops and a preparation method thereof. Background Art

[0002] Pearl eye drops are a clear liquid made from pearl liquid and borneol. The main component of pearl hydrolyzate is pearl, which has the functions of calming the mind, nourishing yin and extinguishing fire, clearing away heat and phlegm, removing cataracts and improving eyesight, and detoxifying and promoting tissue regeneration. Borneol has the functions of opening all orifices, dispersing stagnation, removing cataracts and improving eyesight, and relieving swelling and pain; borneol is easily absorbed by mucous membranes and subcutaneous tissues. Pearl eye drops are mainly used clinically for visual fatigue and chronic conjunctivitis, and can improve symptoms such as eye swelling, itchy eyes, eye pain, dry eyes, and astringent eyes that cannot read for a long time. The borneol component is colorless, transparent or white, translucent, flaky, crisp crystals, which are easily soluble in ethanol, chloroform or ether, but almost insoluble in water. Ethanol or other alcohols are needed to dissolve it in the preparation of eye drops. For example, 3-5 ml of ethanol is added to every 1000 ml in the formula of Chinese application 200410067013.7; 5 ml of propylene glycol is added to every 1000 ml in the formula of Chinese application 201210037634.5; 3-6 ml of butylene glycol is added to every 1000 ml in the formula of Chinese application 201310404998.7. However, alcohols such as ethanol, propylene glycol, and butylene glycol have an inhibitory effect on the central nervous system and a strong stimulating effect. At the same time, the use of high concentrations of ethanol, propylene glycol, butylene glycol and other alcohols in the preparation of large quantities of Pearl Eye Drops requires the production workshop to have explosion-proof functions, which is very costly and has a high safety risk. Even if ethanol is used to dissolve borneol, it is easy to precipitate during the preparation process. The borneol content in Pearl Eye Drops is still relatively low. The quality standard of Pearl Eye Drops is WS. 3 -The borneol content standard in standard B-3281-98-2017 is not less than 0.2 mg per 1 ml, while the actual dosage is 1 mg / ml. Summary of the invention

[0003] In view of the above technical problems, it is positive to study a kind of pearl eye drops that reduce the amount of alcohol excipients and increase the dissolution amount of borneol in the preparation and make it more stable. The inventors have obtained a pearl eye drops in the long-term and extensive research process on pearl eye drops. The eye drops can greatly reduce the amount of alcohol, have a high borneol content, and have extremely high quality stability, increase the safety of medication, and the convenience of production, which is significantly better than the existing technology.

[0004] The technical solution provided by the present invention is:

[0005] Pearl eyesight eye drops are composed of pearl liquid, borneol, poloxamer 188, sodium glycerophosphate, ethanol and water for injection.

[0006] The content of pearl liquid is 2%, the content of borneol is 0.1%, the content of ethanol is 0.15%, the content of poloxamer 188 is 0.002-0.004%, and the content of sodium glycerophosphate is 0.06-0.08%.

[0007] The inventor unexpectedly discovered through a large number of experiments that by adding poloxamer 188 and sodium glycerophosphate, the borneol in the Pearl Eye Drops can be dissolved while significantly reducing the amount of ethanol used. During the preparation process, the borneol does not precipitate and maintains extremely high stability.

[0008] Preferably, the content of poloxamer 188 is 0.003%, and the content of sodium glycerophosphate is 0.07%.

[0009] Preferably, the Pearl Eye Drops may also contain 0.05% ethylparaben and 0.8% sodium chloride.

[0010] Preferably, the specifications of Pearl Eye Drops are 8 ml / tube, 10 ml / tube and 15 ml / tube.

[0011] The present invention also provides a method for preparing pearl eyesight-improving eye drops, comprising the following steps:

[0012] 1. Add poloxamer 188 to ethanol, stir and disperse to dissolve, and obtain the first solution;

[0013] 2. Add borneol to the first liquid and stir to dissolve to obtain the second liquid;

[0014] 3. Add sodium glycerophosphate into water for injection and stir to dissolve to obtain the third solution;

[0015] 4. Slowly add the second liquid into the third liquid while stirring. After adding, add the pearl liquid while stirring, and finally add water for injection to the full amount and stir evenly;

[0016] 5. Filter and sterilize with a 0.22μm filter cartridge and fill into eye drop bottles according to specifications to obtain Pearl Eye Drops.

[0017] The present invention adopts poloxamer 188, sodium glycerophosphate and ethanol as auxiliary materials of Pearl Eye-Ming Eye Drops. The use of the two auxiliary materials, poloxamer 188 and sodium glycerophosphate, can greatly reduce the amount of ethanol while completely dissolving the borneol in the Pearl Eye-Ming Eye Drops, and does not use other alcohols such as propylene glycol. The combined use of the two has an unexpected effect, especially the poloxamer 188 content of 0.003% and the sodium glycerophosphate content of 0.07%. The combination of these two concentrations has the best effect. While dissolving the borneol in the Pearl Eye-Ming Eye Drops, the stability of the Pearl Eye-Ming Eye Drops can be significantly improved.

[0018] The preparation method of the pearl eye drops of the present invention comprises the following steps: firstly mixing and dissolving ethanol and poloxamer 188, then adding borneol and stirring to dissolve, and finally adding the borneol solution to the sodium glycerophosphate solution for mixing. This process step also plays a key role in the preparation of the pearl eye drops. Changing the operation steps will cause the borneol in the pearl eye drops to fail to dissolve smoothly and precipitate during the preparation process. DETAILED DESCRIPTION

[0019] In order to make the present invention easier to understand, specific embodiments of the present invention will be further described below. The specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0020] Example 1 Preparation of Pearl Eye Drops

[0021] Specific preparation method:

[0022] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0023] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0024] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0025] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0026] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0027] Example 2 Preparation of Pearl Eye Drops

[0028] Specific preparation method:

[0029] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0030] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0031] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0032] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0033] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 10ml to obtain Pearl Eye Drops.

[0034] Example 3 Preparation of Pearl Eye Drops

[0035] Specific preparation method:

[0036] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0037] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0038] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0039] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0040] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 15ml to obtain Pearl Eye Drops.

[0041] Example 4 Preparation of Pearl Eye Drops

[0042] Specific preparation method:

[0043] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0044] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0045] 3. Add 7g of sodium glycerophosphate and 5g of ethylparaben to 100ml of water for injection, boil and stir to dissolve, and obtain the third solution;

[0046] 4. Slowly add the second liquid into the third liquid while stirring. After adding, add 200ml pearl liquid and 80g sodium chloride while stirring to dissolve. Finally, add water for injection to a total of 10000ml and stir evenly.

[0047] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0048] Example 5 Preparation of Pearl Eye Drops

[0049] Specific preparation method:

[0050] 1. Add 0.2 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0051] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0052] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0053] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0054] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0055] Example 6 Preparation of Pearl Eye Drops

[0056] Specific preparation method:

[0057] 1. Add 0.4 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0058] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0059] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0060] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0061] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0062] Example 7 Preparation of Pearl Eye Drops

[0063] Specific preparation method:

[0064] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0065] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0066] 3. Add 6g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0067] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0068] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0069] Example 8 Preparation of Pearl Eye Drops

[0070] Specific preparation method:

[0071] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0072] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0073] 3. Add 8g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0074] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0075] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0076] Example 9 Preparation of Pearl Eye Drops

[0077] Specific preparation method:

[0078] 1. Add 0.2 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0079] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0080] 3. Add 6g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0081] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0082] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0083] Example 10 Preparation of Pearl Eye Drops

[0084] Specific preparation method:

[0085] 1. Add 0.4 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0086] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0087] 3. Add 8g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0088] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0089] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0090] Comparative Example 1 Preparation of Pearl Eye Drops

[0091] Specific preparation method:

[0092] 1. Add 0.1 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0093] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0094] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0095] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0096] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0097] Specific preparation test results, referring to the preparation method of the present application, when performing the second step of dissolving borneol, the amount of poloxamer 188 exceeded the scope of the present application, and the borneol could not be completely dissolved.

[0098] Comparative Example 2 Preparation of Pearl Eye Drops

[0099] Specific preparation method:

[0100] 1. Add 0.5 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0101] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0102] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0103] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0104] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0105] Specific preparation test results, referring to the preparation method of the present application, when performing the second step of dissolving borneol, the amount of poloxamer 188 exceeded the scope of the present application, and the borneol could not be completely dissolved.

[0106] Comparative Example 3 Preparation of Pearl Eye Drops

[0107] Specific preparation method:

[0108] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0109] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0110] 3. Add 5g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0111] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0112] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0113] The specific preparation test results refer to the preparation method of this application. When mixing the solutions in step 4, the amount of sodium glycerophosphate exceeds the scope of this application, and the borneol part is analyzed out.

[0114] Comparative Example 4 Preparation of Pearl Eye Drops

[0115] Specific preparation method:

[0116] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0117] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0118] 3. Add 9g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0119] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0120] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0121] The specific preparation test results refer to the preparation method of this application. When mixing the solutions in step 4, the amount of sodium glycerophosphate exceeds the scope of this application, and the borneol part is analyzed out.

[0122] Comparative Example 5 Preparation of Pearl Eye Drops

[0123] Specific preparation method:

[0124] 1. Add 0.3 g of poloxamer 188 into 14 ml of ethanol and stir to dissolve to obtain the first solution;

[0125] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0126] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0127] 4. Slowly add the second liquid to the third liquid while stirring. After adding, add 200ml of pearl liquid while stirring, and finally add water for injection to a total of 10000ml and stir evenly;

[0128] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0129] Specific preparation test results, referring to the preparation method of the present application, when performing the second step of dissolving borneol, the amount of ethanol used exceeds the scope of the present application and the borneol cannot be completely dissolved.

[0130] Comparative Example 6 Preparation of Pearl Eye Drops

[0131] Specific preparation method:

[0132] 1. Add 0.3 g of poloxamer 188 into 15 ml of ethanol and stir to dissolve to obtain the first solution;

[0133] 2. Add 10 g of borneol to the first solution, stir and dissolve to obtain the second solution;

[0134] 3. Add 7g of sodium glycerophosphate into 100ml of water for injection, stir and dissolve to obtain the third solution;

[0135] 4. Slowly add the third liquid into the second liquid while stirring. After adding, add 200ml of pearl liquid while stirring. Finally, add water for injection to a total of 10000ml and stir evenly.

[0136] 5. Filter and sterilize with a 0.22μm filter cartridge, and fill into an eye drop bottle according to the specification of 8ml to obtain Pearl Eye Drops.

[0137] The specific preparation test results refer to the preparation method of the present application. When the solution is mixed in step 4, the solution addition method is changed and the borneol part is analyzed out.

[0138] Judging from the test results of the embodiments and comparative examples (the comparative examples exceed the technical solution conditions of the present application by many means, which are not listed one by one in the present application due to space limitations, and the test results are consistent with the listed comparative examples), the specific dosage of poloxamer 188 and sodium glycerophosphate in the Pearl Eye Drops for Improving Eyes of the present application and the preparation method can successfully prepare the Pearl Eye Drops for Improving Eyes on the basis of reducing the dosage of ethanol. If the technical solution of the present application is exceeded, the Pearl Eye Drops for Improving Eyes cannot be prepared.

[0139] The present invention provides the following test and comparison results:

[0140] Sample 1-10: Pearl eye drops prepared in Example 1-10 of the present invention

[0141] Sample 11: Commercially available pearl eye drops

[0142] Samples 1 to 7 were subjected to accelerated stability tests (40°C ± 2°C, RH 75% ± 5%), and samples were taken at 0, 3, and 6 months. 3 -B-3281-98-2017 inspected the quality indicators. The specific results are shown in Table 1.

[0143] Table 1 Results of accelerated test of Pearl Eye Drops

[0144]

[0145] It can be seen from the results in Table 1 that the pearl eye drops prepared by the present invention have significantly improved borneol content and stability compared with the prior art, and Examples 1-4 have the best stability.

[0146] The above is only a preferred embodiment of the present invention, which certainly cannot be used to limit the scope of rights of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and changes can be made without departing from the principle of the present invention, and these improvements and changes are also regarded as the protection scope of the present invention.

Claims

1. Pearl eye drops, characterized in that It is composed of pearl liquid, borneol, sodium glycerophosphate, ethanol, poloxamer 188 and water for injection.

2. The pearl eye drops as claimed in claim 1, characterized in that: The content of the pearl liquid is 2%, the content of borneol is 0.1%, the content of ethanol is 0.15%, the content of poloxamer 188 is 0.002-0.004%, and the content of sodium glycerophosphate is 0.06-0.08%.

3. The pearl eye drops as claimed in claim 2, characterized in that: The content of Poloxamer 188 is 0.003%.

4. The pearl eye drops as claimed in claim 2, characterized in that: The content of described sodium glycerophosphate is 0.07%.

5. The pearl eye drops according to any one of claim 1, characterized in that: The pearl eyesight-improving eye drops also contain 0.05% ethylparaben and 0.8% sodium chloride.

6. The pearl eye drops according to any one of claims 1 to 5, characterized in that: The specifications of the pearl eye drops are: 8 ml / tube, 10 ml / tube and 15 ml / tube.

7. The method for preparing the pearl eye drops according to any one of claims 1 to 6, characterized in that: The following steps are involved: (1) Add poloxamer 188 to ethanol, stir and disperse to dissolve, and obtain a first solution; (2) Add borneol to the first liquid and stir to dissolve to obtain a second liquid; (3) Add sodium glycerophosphate to water for injection and stir to dissolve to obtain the third solution; (4) Slowly add the second liquid into the third liquid while stirring. After adding, add the pearl liquid while stirring, and finally add water for injection to the full amount and stir evenly; (5) Filter and sterilize with a 0.22 μm filter cartridge and fill into eye drop bottles according to specifications to obtain Pearl Eye Drops.

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