CN115569160A

CN115569160A - Shuanghuanglian eye drops and its preparation method, stability improvement method and extract extraction method

Info

Publication number: CN115569160A
Application number: CN202211229885.3A
Authority: CN
Inventors: 刘继东; 杨强; 李丹; 靳阳; 赵丽丽; 任晓帅
Original assignee: Shenyang Xingqi Pharmaceutical Co Ltd
Current assignee: Shenyang Xingqi Pharmaceutical Co Ltd
Priority date: 2022-10-08
Filing date: 2022-10-08
Publication date: 2023-01-06

Abstract

The invention relates to a method for improving the quality stability of Shuanghuanglian eye drops, which is prepared from extracts of honeysuckle, scutellaria and forsythia. The method comprises the following steps: 1) Extracting honeysuckle, scutellaria and forsythia to obtain corresponding medicinal material extracts for preparing the Shuanghuanglian eye drops; 2) Preparing Shuanghuanglian eye drops by using the obtained medicinal material extract; wherein the method comprises the following steps: -controlling the methamidophos content in at least one medicinal material to be extracted selected from honeysuckle, scutellaria, forsythia or any combination thereof not to be more than 5 μ g/kg, and the omethoate content not to be more than 8 μ g/kg; -extracting the at least one crude drug to be extracted to obtain a crude drug extract thereof for preparing Shuanghuanglian eye drops. The invention also relates to a method for extracting the extract for preparing the Shuanghuanglian eye drops from the medicinal materials, a preparation method of the Shuanghuanglian eye drops and the Shuanghuanglian eye drops.

Description

Shuanghuanglian eye drops and its preparation method, stability improvement method and extract extraction method

Technical Field

The invention relates to the field of medicines, and particularly relates to a method for improving the quality stability of Shuanghuanglian eye drops, a method for extracting an extract for preparing the Shuanghuanglian eye drops from medicinal materials, a preparation method of the Shuanghuanglian eye drops and the Shuanghuanglian eye drops.

Background

The SHUANGHUANGLIAN eye drop has effects of dispelling pathogenic wind, clearing heat, removing toxic substance, and eliminating nebula, and is mainly used for treating herpes simplex caused by pathogenic wind and heat toxin and viral dendritic keratitis. The Shuanghuanglian eye drop medicinal powder is prepared from honeysuckle, scutellaria and forsythia through a series of processes such as extraction, preparation and the like according to the weight ratio of 1; meanwhile, an eye drop solvent was prepared and filled. Before use, the medicinal powder is fully dissolved into an eye drop solvent for use.

The traditional Chinese medicinal materials are easily damaged by diseases and pests in the planting process, and the pesticide is an effective control method. 33 forbidden pesticides are specified in <0212 general inspection rule of medicinal materials and decoction pieces > of Chinese pharmacopoeia (2020 edition), so that the residue of the forbidden pesticides in honeysuckle, scutellaria baicalensis and forsythia suspensa should not appear in principle. However, according to Lijiaxin et al, reported in Chinese medicine journal, 6 months in 2018 and 11 th period in volume 43, ri Jiu Yin et al, ri Jiu Yin (organic phosphorus pesticide) in honeysuckle, some pesticide can still be forbidden.

Furthermore, the present inventors have found that when a honeysuckle flower medicinal material having pesticide residues is used to prepare a shuanghuanglian preparation, the chlorogenic acid content may be reduced.

It is known in the art that chlorogenic acid is one of the main antibacterial and antiviral effective pharmacological components of honeysuckle, and plays an important role in playing the treatment effect of the Shuanghuanglian eye drops. In terms of structure, chlorogenic acid is ester formed by caffeic acid and quinic acid, and three unstable parts of ester bonds, unsaturated double bonds and polyphenol exist in the molecular structure of chlorogenic acid. During the extraction of plants chlorogenic acids tend to undergo transformations by hydrolysis and intramolecular ester group migration. Since chlorogenic acid is the main active ingredient of the Shuanghuanglian eye drops, the reduction of the content of chlorogenic acid can cause the stability of the quality of the eye drops to be influenced.

In the prior art, a Shuanghuanglian ophthalmic gel is disclosed in the patent publication No. CN 100493493C. However, the above patent only discloses the prescription and preparation method of Shuanghuanglian gel, but does not consider the effect of pesticide residue on quality stability.

In addition, although the prescription and preparation method of Shuanghuanglian eye drops are disclosed in the section of Shuanghuanglian eye drops in the Chinese pharmacopoeia (2020 edition), the influence of pesticide residue on the quality stability of eye drops is not studied.

Disclosure of Invention

The present invention has been made in view of the above problems. One scheme of the invention provides a method for improving the quality stability of Shuanghuanglian eye drops, thereby improving the quality stability of the Shuanghuanglian eye drops.

In addition, another embodiment of the present invention provides a method for extracting an extract from a medicinal material for preparing the Shuanghuanglian eye drops, thereby improving the quality stability of the Shuanghuanglian eye drops.

In addition, the invention also provides a preparation method of the Shuanghuanglian eye drops, thereby improving the quality stability of the Shuanghuanglian eye drops.

In addition, the invention also provides Shuanghuanglian eye drops with stable quality.

The inventor finds that the content of chlorogenic acid is remarkably reduced in the case of preparing the Shuanghuanglian preparation by using a medicinal material such as a honeysuckle medicinal material with residual methamidophos and omethoate, and the quality stability of the Shuanghuanglian eye drops can be improved by controlling the content of the methamidophos and the omethoate in the medicinal material such as the honeysuckle medicinal material.

Accordingly, the present invention includes the following embodiments.

1. A method for improving the quality stability of Shuanghuanglian eye drops, which are prepared from the extracts of honeysuckle, scutellaria and forsythia, comprises the following steps:

1) Extracting honeysuckle, scutellaria and forsythia to obtain corresponding medicinal material extracts for preparing the Shuanghuanglian eye drops;

2) Preparing Shuanghuanglian eye drops by using the obtained medicinal material extract;

wherein, step 1) includes:

-controlling the methamidophos content in at least one to-be-extracted medicinal material selected from honeysuckle, scutellaria, forsythia or any combination thereof to be not more than 5 μ g/kg, such as not more than 4 μ g/kg, such as not detected, and the omethoate content to be not more than 8 μ g/kg, such as not more than 6 μ g/kg, such as not detected;

-extracting the at least one medicinal material to be extracted to obtain a medicinal material extract thereof for preparing the Shuanghuanglian eye drops.

2. The method according to item 1, wherein the methamidophos and omethoate content in the at least one crude drug to be extracted is controlled by:

-detecting methamidophos and omethoate content in the at least one drug substance to be extracted;

-extracting if it is detected that the methamidophos content in the at least one crude drug to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, for example not detected, and that the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, for example not detected;

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, such as not detected and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, such as not detected, and then extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

-extracting if it is detected that the methamidophos content in the at least one crude drug to be extracted is not more than 4 μ g/kg, e.g. not detected, and the omethoate content is not more than 6 μ g/kg, e.g. not detected;

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 4 mu g/kg and/or the omethoate content is detected to be more than 6 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mu g/kg, such as undetected methamidophos, and the omethoate content is not more than 6 mu g/kg, such as undetected omethoate, and then extraction is carried out.

3. The method according to item 2, wherein the pesticide residue removal treatment is performed by a carbon dioxide supercritical treatment.

4. The method according to any of items 1-3, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, forsythia suspensa alone, scutellaria baicalensis alone, a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, or a combination of honeysuckle, forsythia suspensa and scutellaria baicalensis.

5. The method according to any of items 1-4, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, honeysuckle in combination with forsythia suspensa, honeysuckle in combination with scutellaria baicalensis, or honeysuckle in combination with forsythia suspensa and scutellaria baicalensis.

6. The method according to any of items 1-5, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, and optionally forsythia suspensa alone and/or scutellaria baicalensis alone.

7. The method according to any of items 1-6, wherein the at least one crude drug to be extracted comprises honeysuckle, such as honeysuckle alone, the method comprising:

-controlling the methamidophos content in the honeysuckle flower medicinal material to be extracted to be not more than 5 mu g/kg, such as not more than 4 mu g/kg, such as not being detected, and the omethoate content to be not more than 8 mu g/kg, such as not more than 6 mu g/kg, such as not being detected;

extracting the honeysuckle medicinal material to be extracted to obtain a honeysuckle extract for preparing the Shuanghuanglian eye drops.

8. The method according to item 7, wherein the at least one medicinal material to be extracted further comprises forsythia suspensa, such as forsythia suspensa alone, and the method further comprises:

-controlling the methamidophos content in the forsythia suspense medicinal material to be extracted to be not more than 5 mug/kg, such as not more than 4 mug/kg, for example, not detected, and the omethoate content to be not more than 8 mug/kg, such as not more than 6 mug/kg, for example, not detected;

extracting the forsythia suspense medicinal material to be extracted or combining and extracting the forsythia suspense medicinal material to be extracted and the honeysuckle medicinal material to be extracted to obtain the extract for preparing the Shuanghuanglian eye drops.

9. The method according to clauses 7 or 8, wherein the at least one crude drug to be extracted further comprises scutellaria baicalensis, such as scutellaria baicalensis alone, and the method further comprises:

-controlling the methamidophos content in the scutellaria baicalensis medicinal material to be extracted as undetected, and controlling the omethoate content as undetected;

-extracting the scutellaria baicalensis medicinal material to be extracted to obtain a scutellaria baicalensis extract for preparing the Shuanghuanglian eye drops.

10. A method for extracting an extract from medicinal materials for preparing Shuanghuanglian eye drops, which are prepared from extracts of honeysuckle flower, scutellaria baicalensis and forsythia suspensa, comprises the following steps:

1) Providing at least one medicinal material to be extracted selected from honeysuckle, scutellaria, forsythia or any combination thereof;

2) Controlling the methamidophos content in the at least one medicinal material to be extracted to be not more than 5 mu g/kg, such as not more than 4 mu g/kg, such as not detected, and the omethoate content to be not more than 8 mu g/kg, such as not more than 6 mu g/kg, such as not detected;

3) And extracting the at least one medicinal material to be extracted to obtain a medicinal material extract for preparing the Shuanghuanglian eye drops.

11. The method according to item 10, wherein methamidophos and omethoate content in the at least one crude drug to be extracted is controlled by:

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, such as undetected, and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, such as undetected, and then extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 4 mug/kg and/or the omethoate content is detected to be more than 6 mug/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mug/kg, for example, is not detected and the omethoate content is not more than 6 mug/kg, for example, is not detected, and then extraction is carried out.

12. The method of clause 11, wherein the pesticide residue removal treatment is performed by carbon dioxide supercritical treatment.

13. The method of any of clauses 10-12, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, forsythia suspensa alone, scutellaria baicalensis alone, a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, or a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis.

14. The method according to any one of items 10-13, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, honeysuckle in combination with forsythia suspensa, honeysuckle in combination with scutellaria baicalensis, or honeysuckle in combination with forsythia suspensa and scutellaria baicalensis.

15. The method according to any of items 10-14, wherein the at least one crude drug to be extracted comprises or is honeysuckle alone, and optionally forsythia suspensa alone and/or scutellaria baicalensis alone.

16. A preparation method of Shuanghuanglian eye drops, which is prepared from extracts of honeysuckle, scutellaria and forsythia, comprises the following steps:

1) Extracting honeysuckle, scutellaria and forsythia to obtain corresponding medicinal material extracts;

wherein at least one selected from the group consisting of: honeysuckle extract, scutellaria extract, forsythia extract, or a combination thereof; preferably, the extract of honeysuckle, the extract of forsythia suspensa, the extract of scutellaria baicalensis, the extract of a combination of honeysuckle and forsythia suspensa, the extract of a combination of honeysuckle and scutellaria baicalensis, the extract of a combination of forsythia suspensa and scutellaria baicalensis, and/or the extract of a combination of honeysuckle, forsythia suspensa and scutellaria baicalensis; preferably, the extract of honeysuckle, the extract of the combination of honeysuckle and forsythia suspensa, the extract of the combination of honeysuckle and scutellaria baicalensis, and/or the extract of the combination of honeysuckle, forsythia suspensa and scutellaria baicalensis; preferably, the extract of honeysuckle flower, and/or the extract of the combination of honeysuckle flower and forsythia fruit.

17. An eye drop of Shuanghuanglian, which is prepared by the method of any item 1 to 16.

In the invention, by controlling the contents of methamidophos and omethoate in medicinal materials, particularly controlling the contents of methamidophos and omethoate in honeysuckle medicinal materials, the influence of methamidophos and omethoate on chlorogenic acid in the extraction process can be effectively reduced, the content of the chlorogenic acid in the Shuanghuanglian eye drop preparation is improved, the condition that the content of the chlorogenic acid in the Shuanghuanglian eye drop is reduced or unqualified due to methamidophos and omethoate is avoided, and the quality stability of the Shuanghuanglian eye drop is effectively improved.

Detailed Description

In the present invention, unless otherwise specified, the term "non-detection" means a concentration lower than the detection limit of the detection instrument used in the detection method of the embodiment of the present invention, and usually less than 3 times the signal-to-noise ratio.

The first aspect of the invention relates to a method for improving the quality stability of Shuanghuanglian eye drops, which is prepared from extracts of honeysuckle, scutellaria and forsythia, and comprises the following steps:

wherein, step 1) includes:

-controlling the methamidophos content in at least one crude drug to be extracted selected from honeysuckle, scutellaria, forsythia or any combination thereof to be not more than 5 μ g/kg, such as not more than 4 μ g/kg, such as not being detected, and the omethoate content to be not more than 8 μ g/kg, such as not more than 6 μ g/kg, such as not being detected;

-extracting the at least one crude drug to be extracted to obtain a crude drug extract thereof for preparing Shuanghuanglian eye drops.

In some embodiments of the first aspect of the present invention, the at least one herb to be extracted may include or be honeysuckle alone, forsythia suspensa alone, scutellaria baicalensis alone, a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, or a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis. Preferably, the at least one herb to be extracted may include or be honeysuckle alone, a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, or a combination of honeysuckle, forsythia and scutellaria. Preferably, the at least one herb to be extracted may comprise or be honeysuckle alone, and optionally, forsythia suspensa alone and/or scutellaria baicalensis alone. For example, the at least one herb to be extracted may include or be honeysuckle alone.

In other words, in some embodiments of the first aspect of the invention, the method may be performed on honeysuckle alone, forsythia alone, scutellaria alone, a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, a combination of forsythia and scutellaria, or a combination of honeysuckle and forsythia and scutellaria. For example, the method may be performed on honeysuckle alone, forsythia alone, and scutellaria alone, respectively; or respectively carrying out the combination of the honeysuckle and the forsythia and the scutellaria; or the fructus forsythiae alone and the combination of the honeysuckle and the scutellaria baicalensis are respectively carried out; or the combination of the single scutellaria baicalensis and the honeysuckle and the forsythia suspensa is respectively carried out; or the combination of honeysuckle, forsythia and scutellaria. Of course, it will also be appreciated by those skilled in the art that the method may be performed on either honeysuckle alone, forsythia alone, and/or scutellaria alone, or any combination thereof, such as a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, a combination of forsythia and scutellaria, and/or a combination of honeysuckle and forsythia and scutellaria. For example, the method is performed on honeysuckle alone, in combination with forsythia suspensa and/or scutellaria baicalensis, such as a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, or a combination of honeysuckle, forsythia suspensa and scutellaria baicalensis.

In the present invention, the methamidophos content in the at least one crude drug to be extracted is controlled to be not more than 5 μ g/kg and the omethoate content is not more than 8 μ g/kg before extraction. Preferably, in the present invention, the methamidophos content in the at least one crude drug to be extracted is controlled to be not more than 4 μ g/kg and omethoate content is not more than 6 μ g/kg before extraction.

In some embodiments of the first aspect of the present invention, the methamidophos content in the at least one crude drug to be extracted may be controlled to be not more than 5.0 μ g/kg, such as not more than: 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9, 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1 μ g/kg, or controlled to be undetectable, even about 0 μ g/kg.

In some embodiments of the first aspect of the present invention, the omethoate content in the at least one crude drug to be extracted may be controlled to be not more than 8.0 μ g/kg, such as not more than: 7.9, 7.8, 7.7, 7.6, 7.5, 7.4, 7.3, 7.2, 7.1, 7.0, 6.9, 6.8, 6.7, 6.6, 6.5, 6.4, 6.3, 6.2, 6.1, 6.0, 5.9, 5.8, 5.7, 5.6, 5.5, 5.4, 5.3, 5.2, 5.1, 5.0, 4.9, 4.8, 4.7, 4.6, 4.5, 4.4, 4.3, 4.2, 4.1, 4.0, 3.9 3.8, 3.7, 3.6, 3.5, 3.4, 3.3, 3.2, 3.1, 3.0, 2.9, 2.8, 2.7, 2.6, 2.5, 2.4, 2.3, 2.2, 2.1, 2.0, 1.9, 1.8, 1.7, 1.6, 1.5, 1.4, 1.3, 1.2, 1.1, 1.0, 0.9, 0.8, 0.7, 0.6, 0.5, 0.4, 0.3, 0.2, 0.1. Mu.g/kg, or is controlled to be undetected, even about 0. Mu.g/kg.

In some embodiments of the first aspect of the present invention, the methamidophos and omethoate content in the at least one crude drug to be extracted is controlled by the following steps:

-detecting methamidophos and omethoate content in the at least one medicinal material to be extracted;

-extracting if it is detected that the methamidophos content in the at least one crude drug to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and that the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, or is not detected and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, or is not detected, and then extraction is carried out;

preferably, the first and second liquid crystal display panels are,

-extracting if it is detected that the methamidophos content in the at least one crude drug to be extracted is not more than 4 μ g/kg or not detected and the omethoate content is not more than 6 μ g/kg or not detected;

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 4 mu g/kg and/or the omethoate content is detected to be more than 6 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mu g/kg or is not detected and the omethoate content is not more than 6 mu g/kg or is not detected, and then extraction is carried out.

In one embodiment of the first aspect of the present invention, the medicinal material to be extracted includes or is the single honeysuckle, the combination of honeysuckle and forsythia, the combination of honeysuckle and scutellaria, or the combination of honeysuckle, forsythia and scutellaria. Thus, in this embodiment, step 1) of the method comprises:

-controlling methamidophos content in at least one drug substance to be extracted selected from honeysuckle alone, combination of honeysuckle with forsythia suspensa, combination of honeysuckle with scutellaria baicalensis, or combination of honeysuckle with forsythia suspensa and scutellaria baicalensis to be no more than 5 μ g/kg, such as no more than 4 μ g/kg, or not detected, and omethoate content to be no more than 8 μ g/kg, such as no more than 6 μ g/kg, or not detected;

-extracting the at least one drug substance to be extracted to obtain a drug substance extract thereof for preparing Shuanghuanglian eye drops;

preferably, the content of methamidophos and omethoate in the at least one medicinal material to be extracted is controlled by the following steps:

preferably, the first and second liquid crystal display panels are,

In some embodiments of the first aspect of the present invention, the medicinal material to be extracted includes honeysuckle, for example, including or being the sole honeysuckle. Thus, in this embodiment, step 1) of the method comprises:

-controlling the methamidophos content in the honeysuckle flower medicinal material to be extracted to be not more than 5 mug/kg, such as not more than 4 mug/kg, or not detected, and the omethoate content to be not more than 8 mug/kg, such as not more than 6 mug/kg, or not detected;

-extracting the honeysuckle flower medicinal material to be extracted to obtain a honeysuckle flower medicinal material extract for preparing the Shuanghuanglian eye drops;

preferably, the contents of methamidophos and omethoate in the honeysuckle medicinal material to be extracted are controlled through the following steps:

-detecting methamidophos and omethoate content in the honeysuckle medicinal material to be extracted;

-extracting if it is detected that methamidophos content in said honeysuckle flower drug to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg or not detected, and omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg or not detected;

if the methamidophos content in the honeysuckle medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, or is not detected and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, or is not detected, and then extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

-if it is detected that the methamidophos content in the honeysuckle flower medicinal material to be extracted is not more than 4 mug/kg or is not detected, and the omethoate content is not more than 6 mug/kg or is not detected, extracting;

if the content of methamidophos in the honeysuckle medicinal material to be extracted is detected to be more than 4 mug/kg and/or the content of omethoate is detected to be more than 6 mug/kg, pesticide residue removing treatment is firstly carried out until the content of methamidophos is not more than 4 mug/kg or no detection is carried out and the content of omethoate is not more than 6 mug/kg or no detection is carried out, and then extraction is carried out.

In some embodiments of the first aspect of the present invention, alternatively or additionally, the at least one herb to be extracted comprises or is forsythia suspensa alone, a combination of honeysuckle and forsythia suspensa, a combination of forsythia suspensa and scutellaria baicalensis, a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis. Accordingly, in the present invention, forsythia suspensa may be treated according to the above-described method, or may be treated according to the above-described method in addition to honeysuckle flower.

Thus, in some embodiments, alternatively or additionally, the method comprises:

-controlling the methamidophos content of at least one of the medicinal materials to be extracted selected from forsythia suspensa alone, a combination of forsythia suspensa and honeysuckle, a combination of forsythia suspensa and scutellaria baicalensis, a combination of forsythia suspensa, honeysuckle and scutellaria baicalensis to be not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and the omethoate content to be not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

-extracting the at least one crude drug to be extracted to obtain a crude drug extract thereof for preparing Shuanghuanglian eye drops;

-extracting if it is detected that the methamidophos content in said at least one crude drug to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg or not detected, and that the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg or not detected;

preferably, the first and second electrodes are formed of a metal,

In some embodiments of the first aspect of the invention, alternatively or additionally, the medicinal material to be extracted comprises forsythia suspensa, for example comprising or being forsythia suspensa alone. Thus, in this embodiment, alternatively or additionally, the method comprises:

-controlling the methamidophos content in the forsythia suspense medicinal material to be extracted to be not more than 5 mug/kg, such as not more than 4 mug/kg, or not detected, and the omethoate content to be not more than 8 mug/kg, such as not more than 6 mug/kg, or not detected;

extracting the forsythia suspense medicinal material to be extracted or performing combined extraction on the forsythia suspense medicinal material to be extracted and a honeysuckle medicinal material to be extracted (namely, under the condition of combined extraction, mixing the honeysuckle subjected to content control of methamidophos and omethoate with the forsythia suspense subjected to content control of methamidophos and omethoate, and then performing extraction) to obtain an extract for preparing the Shuanghuanglian eye drops;

preferably, the content of methamidophos and omethoate in the forsythia suspense medicinal material to be extracted is controlled through the following steps:

-detecting the contents of methamidophos and omethoate in the fructus forsythiae medicinal material to be extracted;

-extracting if it is detected that methamidophos content in the forsythia suspense medicinal material to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

if the content of methamidophos in the forsythia suspense medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the content of omethoate is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the content of methamidophos is not more than 5 mu g/kg, such as not more than 4 mu g/kg, or is not detected and the content of omethoate is not more than 8 mu g/kg, such as not more than 6 mu g/kg, or is not detected, and then extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

-if it is detected that the methamidophos content in the forsythia suspense medicinal material to be extracted is not more than 4 mug/kg or is not detected, and the omethoate content is not more than 6 mug/kg or is not detected, extracting;

if the methamidophos content in the forsythia suspense medicinal material to be extracted is detected to be more than 4 mu g/kg and/or the omethoate content is detected to be more than 6 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mu g/kg or is not detected and the omethoate content is not more than 6 mu g/kg or is not detected, and then extraction is carried out.

In some embodiments of the first aspect of the present invention, alternatively or additionally, the at least one herb to be extracted comprises or is scutellaria baicalensis alone, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis. Thus, in the present invention, scutellaria may be treated according to the above-described method, or alternatively, in addition to honeysuckle, according to the above-described method, scutellaria may be treated according to the above-described method, or alternatively, in addition to forsythia, according to the above-described method, scutellaria may be treated according to the above-described method, or alternatively, scutellaria may be treated according to the above-described method, in addition to honeysuckle and scutellaria.

Thus, in some embodiments, alternatively or additionally, the method comprises:

-controlling methamidophos content in at least one crude drug to be extracted selected from scutellaria baicalensis alone, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, and a combination of honeysuckle, forsythia suspensa and scutellaria baicalensis to be not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and omethoate content not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

preferably, the first and second liquid crystal display panels are,

In some embodiments of the first aspect of the present invention, alternatively or additionally, the medicinal material to be extracted comprises scutellaria baicalensis, for example comprising or being scutellaria baicalensis alone. Thus, in this embodiment, alternatively or additionally, the method comprises:

-extracting the scutellaria baicalensis medicinal material to be extracted to obtain a forsythia suspense medicinal material extract for preparing the Shuanghuanglian eye drops;

-detecting the contents of methamidophos and omethoate in the scutellaria baicalensis medicinal material to be extracted;

-extracting if it is detected that the methamidophos content in the scutellaria baicalensis medicinal material to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

if the methamidophos content in the scutellaria baicalensis medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, or is not detected and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, or is not detected, and then extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

-extracting if it is detected that the methamidophos content in the scutellaria baicalensis medicinal material to be extracted is not more than 4 μ g/kg or not detected and the omethoate content is not more than 6 μ g/kg or not detected;

if the content of methamidophos in the scutellaria baicalensis medicinal material to be extracted is detected to be more than 4 mu g/kg and/or the content of omethoate is detected to be more than 6 mu g/kg, pesticide residue removing treatment is firstly carried out until the content of methamidophos is not more than 4 mu g/kg or is not detected and the content of omethoate is not more than 6 mu g/kg or is not detected, and then extraction is carried out.

In some embodiments of the first aspect of the present invention, the pesticide residue removal treatment is performed by carbon dioxide supercritical treatment (i.e. treatment with supercritical carbon dioxide), or by soaking with water as a solvent at normal temperature.

The extraction step may be performed by any suitable method known in the art as long as the effective ingredients for preparing the shuanghuanglian eye drops can be efficiently extracted. The extraction step may be performed using any suitable known solvent, such as water, ethanol, and the like.

In some embodiments of the first aspect of the present invention, the extraction of the individual honeysuckle flower medicinal material may be performed, for example, by: optionally soaking with water (e.g. at room temperature) and then extracting at a temperature above room temperature, e.g. by decoction with water once, twice or more times; filtering (e.g. combined) extract(s), e.g. decoction, concentrating to remove water; extracting with ethanol, concentrating the extractive solution to remove ethanol, extracting with water, concentrating the extractive solution to remove water, extracting with ethanol, and concentrating the extractive solution to remove ethanol.

In some embodiments of the first aspect of the present invention, the extraction of the individual honeysuckle flower medicinal material may be performed, for example, by a section of "chinese pharmacopoeia" (2020 edition): the preparation of the prescription is carried out by the method described in the section of Shuanghuanglian eye drops (page 778). In some embodiments of the first aspect of the present invention, the extraction method for the individual honeysuckle flowers may be performed, for example, as follows: soaking honeysuckle in water for 30 minutes, decocting twice, each time for 1 hour, mixing decoctions, filtering, concentrating the filtrate to obtain a clear paste with the relative density of 1.20-1.25 (70 ℃), cooling to 40 ℃, slowly adding ethanol to make the alcohol content reach 75%, fully stirring, standing for 12 hours, filtering to obtain a supernatant, recovering ethanol until no alcohol smell exists, adding water, standing for 12 hours, filtering to obtain a supernatant, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (80 ℃), cooling to 40 ℃, adding ethanol to make the alcohol content reach 85%, standing for more than 12 hours, filtering to obtain a supernatant, recovering ethanol until no alcohol smell exists, and obtaining the extract.

The method for extracting the honeysuckle flower medicinal material is not limited to the above method, as long as the effective components for preparing the Shuanghuanglian eye drops can be effectively extracted.

In some embodiments of the first aspect of the present invention, the extraction of the individual forsythia suspense medicinal material may be performed, for example, by: optionally macerating with water (e.g. at room temperature) and then extracting at a temperature above room temperature, e.g. by decoction with water once, twice or more; filtering (e.g. combined) extract(s), e.g. decoction, concentrating to remove water; extracting with ethanol, concentrating the extractive solution to remove ethanol, extracting with water, concentrating the extractive solution to remove water, extracting with ethanol, and concentrating the extractive solution to remove ethanol.

In some embodiments of the first aspect of the invention, the extraction of the individual forsythia suspense medicinal material may be performed, for example, by the section "chinese pharmacopoeia" (2020 edition): the method described in the section of eye drops of the adult formulation and the single formulation of Shuanghuanglian (page 778). In some embodiments of the first aspect of the invention, the extraction process for forsythia suspensa alone may be performed, for example, as follows: soaking fructus forsythiae in water for 30 minutes, decocting twice, each time for 1 hour, mixing decoctions, filtering, concentrating the filtrate to obtain a clear paste with the relative density of 1.20-1.25 (70 ℃), cooling to 40 ℃, slowly adding ethanol to ensure that the alcohol content reaches 75%, fully stirring, standing for 12 hours, filtering to obtain a supernatant, recovering ethanol until no alcohol smell exists, adding water, standing for 12 hours, filtering to obtain a supernatant, concentrating to obtain a clear paste with the relative density of 1.10-1.15 (80 ℃), cooling to 40 ℃, adding ethanol to ensure that the alcohol content reaches 85%, standing for more than 12 hours, filtering to obtain a supernatant, and recovering ethanol until no alcohol smell exists, thus obtaining the extract.

The method for extracting forsythia suspense is not limited to this, as long as the effective components for preparing the shuanghuanglian eye drops can be effectively extracted.

In some embodiments of the first aspect of the present invention, the extraction of individual scutellaria baicalensis medicinal materials may be performed, for example, by: optionally soaking with water (e.g. at room temperature) and then extracting at a temperature above room temperature, e.g. decocting with water once, twice or more, filtering the (e.g. combined) extract, e.g. decoction, adjusting the pH (e.g. to 1.0 to 2.0) with an acid (e.g. hydrochloric acid), filtering, mixing the precipitate with water, adjusting the pH (e.g. to neutral, e.g. equal to or below 7.0, e.g. 6.0 to 7.0) with a base (e.g. NaOH), adding ethanol, mixing dissolving the filtration, adjusting the pH (e.g. to 1.0 to 2.0) with an acid (e.g. hydrochloric acid) and filtering, washing the precipitate with ethanol (e.g. to pH 4.0), adding water, adjusting the pH (e.g. to neutral, e.g. to equal to or below 7.0, e.g. 6.0 to 7.0), mixing with activated carbon, then adding ethanol and filtering after mixing the filtrate, adjusting the pH (e.g. to 1.0 to 2.0) with an acid, filtering, washing the precipitate with ethanol and drying.

In some embodiments of the first aspect of the invention, the extraction of individual scutellaria baicalensis medicinal materials can be performed, for example, by the section of the chinese pharmacopoeia (2020 edition): the method described in the section of eye drops of the adult formulation and the single formulation of Shuanghuanglian (page 778). In some embodiments of the first aspect of the invention, the extraction process for individual scutellaria baicalensis may be performed, for example, as follows: decocting scutellaria baicalensis twice with water, each time for 1 hour, combining and filtering, adjusting the pH value of filtrate to 1.0-2.0 by using 2mol/L hydrochloric acid solution, preserving heat for 30 minutes at 80 ℃, standing for 24 hours, filtering, adding water into precipitates, stirring, adjusting the pH value to 6.0-7.0 by using 40% sodium hydroxide solution, adding equal amount of ethanol, stirring to dissolve, filtering, adjusting the pH value of filtrate to 2.0 by using 2mol/L hydrochloric acid solution, preserving heat for 30 minutes at 80 ℃, standing for 12 hours, filtering, washing precipitates to 4.0 by using ethanol, adding water, stirring, adjusting the pH value to 6.0-7.0 by using 40% sodium hydroxide solution, adding 0.5% active carbon, fully stirring, preserving heat for 30 minutes at 50 ℃, adding ethanol, stirring uniformly, filtering immediately, adjusting the pH value of filtrate to 2.0 by using 2mol/L hydrochloric acid solution, preserving heat for 30 minutes at 80 ℃, standing for 12 hours, filtering, washing precipitates by using a small amount of ethanol, and drying at the temperature of below 60 ℃ to obtain the extract.

The extraction method of the scutellaria baicalensis medicinal material is not limited to the method, and the effective components for preparing the Shuanghuanglian eye drops can be effectively extracted.

As described above, the present invention may also extract a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, a combination of forsythia and scutellaria, or a combination of honeysuckle, forsythia and scutellaria.

For example, in some embodiments of the first aspect of the present invention, the extraction may be performed on a combination of honeysuckle and forsythia suspensa.

The extraction of the combination (i.e. mixture) of honeysuckle and forsythia suspensa may be performed, for example, by: optionally macerating with water (e.g. at room temperature) and then extracting at a temperature above room temperature, e.g. by decoction with water once, twice or more; filtering (e.g. combined) extract (e.g. decoction), concentrating to remove water; extracting with ethanol, concentrating the extractive solution to remove ethanol, extracting with water, concentrating the extractive solution to remove water, extracting with ethanol, and concentrating the extractive solution to remove ethanol.

In some embodiments of the first aspect of the invention, the extraction of the combination of honeysuckle and forsythia suspensa may be performed, for example, by a section of the chinese pharmacopoeia (2020 edition): the method described in the section of eye drops of the adult formulation and the single formulation of Shuanghuanglian (page 778). In some embodiments of the first aspect of the present invention, the extraction method for the combination of honeysuckle and forsythia suspensa may be performed, for example, as follows: soaking honeysuckle and forsythia suspense in water for 30 minutes respectively, decocting twice, each time lasting for 1 hour, merging decoction, filtering, concentrating filtrate to obtain clear paste with the relative density of 1.20-1.25 (70 ℃), cooling to 40 ℃, slowly adding ethanol to ensure that the alcohol content reaches 75%, fully stirring, standing for 12 hours, filtering supernatant, recovering ethanol until no alcohol smell exists, adding water, standing for 12 hours, filtering supernatant, concentrating to obtain clear paste with the relative density of 1.10-1.15 (80 ℃), cooling to 40 ℃, adding ethanol to ensure that the alcohol content reaches 85%, standing for more than 12 hours, filtering supernatant, recovering ethanol until no alcohol smell exists, and obtaining the extract.

The extraction method of the combination of honeysuckle and forsythia is not limited thereto, as long as the effective ingredients for preparing the shuanghuanglian eye drops can be effectively extracted.

In the present invention, the removal of pesticide residues and extraction may be performed, for example, but not limited to, as follows:

(1) Respectively carrying out pesticide residue removal treatment on the single honeysuckle, the single scutellaria baicalensis and the single forsythia suspense, and then respectively extracting;

(2) Respectively carrying out pesticide residue removal treatment on the single honeysuckle, the single scutellaria and the single forsythia, and then extracting the medicinal material combination (such as the combination of the honeysuckle and the forsythia, the combination of the honeysuckle and the scutellaria, the combination of the forsythia and the scutellaria, or the combination of the honeysuckle, the forsythia and the scutellaria) subjected to pesticide residue removal treatment;

(3) Removing pesticide residues from flos Lonicerae, scutellariae radix, and fructus forsythiae (such as flos Lonicerae and fructus forsythiae combination, flos Lonicerae and Scutellariae radix combination, fructus forsythiae and Scutellariae radix combination, or flos Lonicerae, fructus forsythiae and Scutellariae radix combination), and extracting the pesticide residue removed combination;

or

(4) Any combination of (1) to (3) above.

In some embodiments of the first aspect of the present invention, the methamidophos content in the at least one crude drug to be extracted selected from the group consisting of honeysuckle, scutellaria baicalensis, forsythia suspensa or any combination thereof originally provided in step 1) is greater than 5 μ g/kg, and/or the omethoate content is greater than 8 μ g/kg. In some embodiments of the first aspect of the present invention, the methamidophos content in the at least one crude drug to be extracted selected from the group consisting of honeysuckle, scutellaria baicalensis, forsythia suspensa or any combination thereof originally provided in step 1) is greater than 4 μ g/kg, and/or the omethoate content is greater than 6 μ g/kg. For example, the methamidophos content in the honeysuckle medicinal material to be extracted is more than 4 mug/kg, and/or the omethoate content is more than 6 mug/kg; when the content of methamidophos in the forsythia suspense medicinal material is more than 4 mu g/kg, and/or the content of omethoate is more than 6 mu g/kg; and/or the methamidophos content in the medicinal material of the scutellaria baicalensis to be extracted is more than 4 mu g/kg, and/or the omethoate content is more than 6 mu g/kg. In other words, the invention can use medicinal materials containing the high methamidophos and omethoate pesticide residues to prepare the Shuanghuanglian eye drops with stable quality.

The second aspect of the present invention relates to a method for extracting an extract from a medicinal material for preparing a Shuanghuanglian eye drop, which is prepared from extracts of honeysuckle, scutellaria and forsythia, the method comprising:

2) Controlling the methamidophos content in the at least one medicinal material to be extracted to be not more than 5 mu g/kg, such as not more than 4 mu g/kg, or not detected, and the omethoate content to be not more than 8 mu g/kg, such as not more than 6 mu g/kg, or not detected;

In some embodiments of the second aspect of the present invention, the method controls methamidophos and omethoate content in the at least one crude drug to be extracted by:

-detecting methamidophos and omethoate content in the medicinal material to be extracted;

-extracting if it is detected that the methamidophos content in the drug substance to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, or not detected, and the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, or not detected;

if the methamidophos content in the medicinal material to be extracted is detected to be more than 5 mu g/kg and/or the omethoate content is detected to be more than 8 mu g/kg, the pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 5 mu g/kg, such as not more than 4 mu g/kg, or is not detected and the omethoate content is not more than 8 mu g/kg, such as not more than 6 mu g/kg, or is not detected, and then the extraction is carried out;

preferably, the first and second electrodes are formed of a metal,

-if it is detected that the methamidophos content in the medicinal material to be extracted is not more than 4 μ g/kg or not detected and the omethoate content is not more than 6 μ g/kg or not detected, performing extraction;

if the methamidophos content in the medicinal materials to be extracted is detected to be more than 4 mu g/kg and/or the omethoate content is detected to be more than 6 mu g/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mu g/kg or is not detected and the omethoate content is not more than 6 mu g/kg or is not detected, and then extraction is carried out.

In some embodiments of the second aspect of the present invention, the pesticide residue removal treatment is performed by carbon dioxide supercritical treatment, or by soaking with water as a solvent at normal temperature.

In some embodiments of the second aspect of the present invention, the at least one herb to be extracted comprises or is honeysuckle alone, forsythia suspensa alone, scutellaria baicalensis alone, a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, or a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis; preferably, the at least one medicinal material to be extracted comprises or is the single honeysuckle, the combination of the honeysuckle and the forsythia, the combination of the honeysuckle and the scutellaria or the combination of the honeysuckle, the forsythia and the scutellaria; preferably, the at least one herb to be extracted comprises or is honeysuckle alone, and optionally, forsythia alone and/or scutellaria alone. For example, the at least one herb to be extracted may include or be honeysuckle alone.

In other words, the method of the second aspect of the present invention may be used to extract the respective extracts from honeysuckle alone, forsythia alone, and scutellaria alone, respectively. The corresponding extract may also be extracted from any combination thereof (e.g., a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, a combination of forsythia and scutellaria, or a combination of honeysuckle, forsythia and scutellaria).

The above description of the method of the first aspect also applies to the method of the second aspect.

The third aspect of the invention relates to a preparation method of Shuanghuanglian eye drops, which is prepared from extracts of honeysuckle, scutellaria and forsythia and comprises the following steps:

wherein at least one selected from the group consisting of: honeysuckle extract, scutellaria extract, forsythia extract, or a combination thereof.

In some embodiments of the third aspect of the present invention, at least one selected from the group consisting of: honeysuckle extract, forsythia extract, scutellaria extract, a combination of honeysuckle and forsythia extract, a combination of honeysuckle and scutellaria extract, a combination of forsythia and scutellaria extract, and/or a combination of honeysuckle, forsythia and scutellaria extract.

In some embodiments of the third aspect of the present invention, at least one selected from the group consisting of: honeysuckle extract, honeysuckle and forsythia extract, honeysuckle and scutellaria extract, and/or honeysuckle, forsythia and scutellaria extract.

In some embodiments of the third aspect of the present invention, the extract of honeysuckle flower, and/or the extract of a combination of honeysuckle flower and forsythia suspensa, is prepared by a method according to any of the embodiments of the first or second aspect.

The above description regarding the first and second aspects also applies to this third aspect.

A fourth aspect of the present invention relates to a shuanghuanglian eye drop prepared by the method according to the first, second or third aspect.

In particular, the fourth aspect of the present invention includes, but is not limited to, the following:

-combining the prepared honeysuckle extract, forsythia extract, scutellaria extract and formulated as a shuanghuanglian eye drop, when the honeysuckle alone, forsythia extract alone, scutellaria extract alone are extracted according to the method of the first, second or third aspect, respectively.

-when extracting the combination of honeysuckle and forsythia suspensa, scutellaria baicalensis alone, according to the method of the first, second, or third aspect, respectively, combining the prepared extract of the combination of honeysuckle and forsythia suspensa, with the extract of scutellaria baicalensis and formulating into a shuanghuanglian eye drop.

-when extracting the combination of honeysuckle and scutellaria, forsythia suspensa alone, according to the method of the first, second or third aspect, respectively, combining the prepared extract of honeysuckle and scutellaria, with forsythia suspensa extract and formulating into a shuanghuanglian eye drop.

-combining the prepared honeysuckle extract, the combined forsythia extract and scutellaria extract and formulating into a shuanghuanglian eye drop, when the honeysuckle alone, the scutellaria baicalensis and the forsythia suspensa are extracted according to the method of the first, second or third aspect, respectively.

-when the combination of honeysuckle and forsythia and scutellaria is extracted according to the method of the first, second or third aspect, the prepared extract of the combination of honeysuckle and forsythia and scutellaria is formulated into shuanghuanglian eye drops.

Methods for preparing Shuanghuanglian eye drops by using the above medicinal material extracts are well known in the art. It can be carried out, for example, according to the method described in patent CN1220501C of the present applicant.

The inventor finds that by using the method to prepare the Shuanghuanglian eye drops, because the content of methamidophos and the content of omethoate in honeysuckle, forsythia and/or scutellaria are controlled before extraction, the influence of methamidophos and omethoate on chlorogenic acid in the extraction process can be effectively reduced, and the influence of residual methamidophos and omethoate on the chlorogenic acid in the Shuanghuanglian eye drops can be avoided, so that the situation that the content of chlorogenic acid in the Shuanghuanglian eye drops is reduced or unqualified due to the methamidophos and the omethoate is avoided, and the content of the chlorogenic acid in different batches of products is basically kept consistent.

Examples

The following examples are given to illustrate the present invention and should not be construed as limiting the scope of the present invention.

For the purpose of laboratory research, the inventor researches the influence of methamidophos and omethoate pesticide residues in three traditional Chinese medicinal materials on the content of chlorogenic acid and the stability of the eye drops, determines the maximum theoretical residual limit of methamidophos and omethoate in honeysuckle, scutellaria baicalensis and forsythia suspensa through a large amount of experimental researches, and ensures that the effective content of the chlorogenic acid is not influenced, so that the stability of the eye drops is not influenced.

In the following examples, the present inventors purchased honeysuckle flowers produced in Shandong and Hubei, scutellaria baicalensis produced in inner Mongolia and Shanxi, and Forsythia suspensa produced in Henan and Shanxi, respectively, and examined the contents of chlorogenic acid, methamidophos and omethoate in the medicinal materials by the following methods, and conducted the following tests.

Experimental example 1 influence of pesticide residue in honeysuckle on chlorogenic acid:

experiments 1-1 respectively select and use methamidophos and omethoate for extraction, and investigate the influence of the existence of the two pesticide residues on chlorogenic acid in the honeysuckle extraction process.

The extraction process is as follows: soaking 250g of honeysuckle in water for 30 minutes, decocting twice, each time for 1 hour, mixing decoctions, filtering, concentrating the filtrate to obtain clear paste with the relative density of 1.20-1.25 (70 ℃), cooling to 40 ℃, slowly adding ethanol to ensure that the alcohol content reaches 75%, fully stirring, standing for 12 hours, filtering to obtain supernatant, recovering ethanol until no alcohol smell exists, adding water, standing for 12 hours, filtering to obtain supernatant, concentrating to obtain clear paste with the relative density of 1.10-1.15 (80 ℃), cooling to 40 ℃, adding ethanol to ensure that the alcohol content reaches 85%, standing for more than 12 hours, filtering to obtain supernatant, and recovering ethanol until no alcohol smell exists, thus obtaining the extract.

After the extraction process is finished (namely, the extraction process is finished, the decoction is mixed and filtered for 1 hour each time, the step 1) is finished, the concentration is finished (namely, the extraction process is finished, namely, the filtrate is concentrated to the clear paste with the relative density of 1.20-1.25 (70 ℃), the step 2) is finished, 75% of alcohol precipitation and concentration are finished (namely, the extraction process is cooled to 40 ℃, ethanol is slowly added to ensure that the alcohol content reaches 75%, the full stirring is carried out, the standing is carried out for 12 hours, the supernatant is filtered and concentrated to the clear paste with the relative density of 1.10-1.15 (80 ℃), the step 4) and the 85% alcohol precipitation process is finished (namely, the extraction process is cooled to 40 ℃, ethanol is added to ensure that the alcohol content reaches 85%, the standing is carried out for more than 12 hours, the supernatant is filtered, the ethanol is recovered to ensure that the alcohol content reaches 85%, and the pesticide content and chlorogenic acid content of methylamine phosphate and oxygen in the chlorogenic acid in each step 5) are detected.

The methamidophos and omethoate detection method comprises the following steps: reference is made to the following documents: method for evaluating residue status and risk of organic phosphorus pesticide in flos Lonicerae (Lijiaxin, shishanmei, xue Jian, chinese traditional medicine journal, 6 months in 2018, vol.43, 11 th). An Agilent 7890A gas chromatograph (FPD detector), an HP-5 capillary chromatographic column (0.25 μm × 0.32mm × 30 m), a sample inlet temperature of 250 ℃, no split sample injection, a temperature raising program: initial temperature 80 ℃ at 10 ℃ min ^-1 Heating to 170 deg.C, and keeping at 5 deg.C/min ^-1 Heating to 190 deg.C at 2 deg.C/min ^-1 Heating to 200 deg.C at 10 deg.C/min ^-1 Heating to 250 deg.C, and maintaining for 14min; the temperature of the detector is 250 ℃; the carrier gas was nitrogen, constant pressure 6.71psi (1psi = 6.895kpa); hydrogen flow rate of 75 mL/min ^-1 Air flow 60 mL/min ^-1 And the sample amount is 1 mu L, and the quantitative detection is carried out by an external standard method.

The chlorogenic acid detection method comprises the following steps: the method is carried out according to the content determination item of honeysuckle in 'Chinese pharmacopoeia' 2020 annual golden in Shuanghuanglian eye drops. Using high performance liquid chromatography with octadecylsilane chemically bonded silica as filler; with methanol-water-glacial acetic acid (20; the detection wavelength is 324nm, and the quantitative detection is carried out by an external standard method.

The influence of two pesticides methamidophos and omethoate on the chlorogenic acid content in the honeysuckle extraction process is shown in the following table 1:

TABLE 1 influence of Methylphosphine and omethoate residue on chlorogenic acid content in the extraction of Lonicera japonica

Note: "-" indicates undetected or absent.

The result proves that the residue of methamidophos and omethoate can influence the content of the effective substance of honeysuckle in the extraction process, namely chlorogenic acid.

Experiments 1-2 respectively use medicinal materials with different contents of methamidophos and omethoate for extraction, and examine the influence of the residual quantity of the two pesticides on chlorogenic acid in the extraction process of honeysuckle and forsythia suspensa:

the extraction method and the detection method of chlorogenic acid, methamidophos and omethoate are the same as the examples in test 1-1. The influence of the residual quantities of methamidophos and omethoate on the chlorogenic acid content in the honeysuckle extraction process is shown in the following table 2:

TABLE 2 influence of different residual quantities of methamidophos and omethoate on chlorogenic acid content in the extraction of honeysuckle flower

The above example results demonstrate that:

(1) The more the two pesticides of methamidophos and omethoate are left, the greater the influence on the chlorogenic acid content of the effective substances of the honeysuckle in the extraction process is;

(2) In example 7, when 250g of honeysuckle contains 1.93 μ g of methamidophos and 2.88 μ g of omethoate, that is, the honeysuckle contains 7.72 μ g/kg of methamidophos and 11.52 μ g/kg of omethoate, the influence of pesticide residue on the extraction amount of chlorogenic acid as an effective substance is obviously reduced. In example 8, when 250g of honeysuckle contains 1.04 μ g of methamidophos and 1.61 μ g of omethoate, that is, the honeysuckle contains 4.16 μ g/kg of methamidophos and 6.44 μ g/kg of omethoate, the pesticide residue has no influence on the extraction amount of chlorogenic acid which is an effective substance.

(3) Therefore, when the methamidophos residue in the honeysuckle medicinal material is controlled below 5 mu g/kg, for example, further controlled below 4 mu g/kg, and the omethoate residue is controlled below 8 mu g/kg, for example, further controlled below 6 mu g/kg, the extraction amount of the chlorogenic acid as an effective substance is not influenced basically.

Experimental example 2 influence of pesticide residue in scutellaria baicalensis medicinal material on chlorogenic acid:

the scutellaria baicalensis without methamidophos and omethoate and the scutellaria baicalensis with methamidophos and omethoate are respectively selected and extracted, and the influence of the methamidophos and omethoate pesticide residues contained in the scutellaria baicalensis extract on the chlorogenic acid as the effective component in the preparation process is inspected.

The extraction process of the scutellaria baicalensis comprises the following steps: decocting 250g of scutellaria baicalensis in water twice (8, 6 times of the volume of the scutellaria baicalensis) for 1 hour each time, merging and filtering, adjusting the pH value of filtrate to 1.0-2.0 by using 2mol/L hydrochloric acid solution, preserving heat for 30 minutes at 80 ℃, standing for 24 hours, filtering, adding 8 times of water into precipitate, stirring, adjusting the pH value to 6.0-7.0 by using 40% sodium hydroxide solution, adding equal amount of ethanol, stirring for dissolving, filtering, adjusting the pH value of filtrate to 2.0 by using 2mol/L hydrochloric acid solution, preserving heat for 30 minutes at 80 ℃, standing for 12 hours, filtering, washing precipitate by using ethanol until the pH value is 4.0, adding 10 times of water, stirring, adjusting the pH value to 6.0-7.0 by using 40% sodium hydroxide solution, adding 0.5% active carbon, fully stirring, preserving heat for 30 minutes at 50 ℃, adding 1-2 times of ethanol, stirring uniformly, immediately filtering, adjusting the pH value of filtrate by using 2mol/L hydrochloric acid solution until the pH value is 2.0, preserving heat for 30 minutes at 80 ℃, standing for 12 hours, filtering, washing precipitate by using a small amount of ethanol, and drying at 60 ℃ or below.

After the extraction is finished (i.e., "water is added and decocted twice (8, 6 times) for 1 hour each time in the extraction), the two are combined and filtered", step 1), the first acid precipitation (i.e., "filtrate in the extraction is adjusted to pH 1.0-2.0 by 2mol/L hydrochloric acid solution, kept at 80 ℃ for 30 minutes, kept at rest for 24 hours, filtered", step 2), the second acid precipitation (i.e., "precipitate in the extraction is added with 8 times of water, stirred, adjusted to pH 6.0-7.0 by 40% sodium hydroxide solution, added with equal amount of ethanol, stirred to dissolve, filtered, adjusted to pH 2.0 by 2mol/L hydrochloric acid solution, kept at 80 ℃ for 30 minutes, kept at rest for 12 hours, filtered", step 3) and finally the extract (step 4) are obtained to detect the residue of methamidophos and omethoate, and the results are shown in Table 3. And the obtained scutellaria baicalensis extract is put into the preparation process treatment of the Shuanghuanglian eye drops.

TABLE 3 Methamidophos and omethoate residue status of Scutellariae radix extraction steps

The preparation process of the Shuanghuanglian eye drops comprises the following steps: adding appropriate amount of water into Scutellariae radix extract, heating, adjusting pH to 7.0 with 40% sodium hydroxide solution, dissolving, adding appropriate amount of flos Lonicerae and fructus forsythiae extract, adding water to 200ml, adding 0.5% active carbon, keeping pH at 7.0, heating and boiling for 15 min, cooling, filtering, adding injectable water to full volume, sterilizing at 115 deg.C for 30 min, refrigerating for 1 week, filtering with microporous membrane, concentrating the filtrate, freeze drying, packaging into 200 pieces with 60mg each, and sealing.

The content of methamidophos and omethoate and the content of chlorogenic acid are detected in each step of decarbonization (step 5), sterilization (step 6), refrigeration (step 7) and freeze-drying (step 8) in the preparation process. The results are given in Table 4 below:

TABLE 4 influence of methamidophos and omethoate residues in Scutellariae radix extract on chlorogenic acid in preparation process

In the above example 9, in order to study the influence of methamidophos and omethoate residue on the chlorogenic acid content of the preparation when methamidophos and omethoate are not completely removed in the extraction process of preparing the scutellaria baicalensis extract, a scutellaria baicalensis medicinal material containing a large amount of methamidophos and omethoate was selected. In this example, the residues of methamidophos and omethoate could be controlled to be undetected in the sterilization process (corresponding to step 6) for preparing the preparation, but the residues of methamidophos and omethoate still had an influence on the content of chlorogenic acid in the decarburizing process (corresponding to step 5) of example 9.

The above example results demonstrate that although methamidophos and omethoate residues of scutellaria baicalensis of the shuanghuanglian eye drops can be completely removed in the sterilization process of the preparation, the effective substance chlorogenic acid can still be affected in the preparation before the removal, so that before the honeysuckle extract is added, namely the extraction step 4 of scutellaria baicalensis is required to ensure that the contents of both methamidophos and omethoate of scutellaria baicalensis are not detected. In order to avoid the influence on the content of chlorogenic acid in the preparation, in a specific embodiment of the invention, the contents of methamidophos and omethoate in the medicinal material to be extracted from scutellaria baicalensis are more strictly controlled to be undetected.

Experimental example 3 influence of pesticide residue in Forsythia suspensa on chlorogenic acid

The extraction process of fructus forsythiae is completely the same as that of flos Lonicerae. The process is carried out as follows: soaking 500g of fructus forsythiae in water for 30 minutes, decocting twice, each time for 1 hour, mixing decoctions, filtering, concentrating the filtrate to obtain clear paste with the relative density of 1.20-1.25 (70 ℃), cooling to 40 ℃, slowly adding ethanol to ensure that the alcohol content reaches 75%, fully stirring, standing for 12 hours, filtering to obtain supernatant, recovering ethanol until no alcohol smell exists, adding water, standing for 12 hours, filtering to obtain supernatant, concentrating to obtain clear paste with the relative density of 1.10-1.15 (80 ℃), cooling to 40 ℃, adding ethanol to ensure that the alcohol content reaches 85%, standing for more than 12 hours, filtering to obtain supernatant, recovering ethanol until no alcohol smell exists, thus obtaining the extract.

After the extraction process is finished (namely, the extraction is finished by twice decoction and 1 hour each time, decoction is combined and filtered) and the concentration is finished (namely, the filtrate in the extraction is concentrated to a clear paste with the relative density of 1.20-1.25 (70 ℃), the step 2), 75% of alcohol precipitation and the concentration are finished (namely, the extraction process is cooled to 40 ℃, ethanol is slowly added to ensure that the alcohol content reaches 75%, the mixture is fully stirred and is kept stand for 12 hours, the supernatant is filtered and is recovered until no alcohol taste exists), the step 3 is finished, the water precipitation and the concentration are finished (namely, the extraction process is finished by adding water and keeping stand for 12 hours, the supernatant is filtered and is concentrated to a clear paste with the relative density of 1.10-1.15 (80 ℃), the step 4) and the 85% of alcohol precipitation and the concentration process is finished (namely, the extraction process is cooled to 40 ℃, ethanol is added to ensure that the alcohol content reaches 85%, the standing for more than 12 hours, the supernatant is filtered and the pesticide content of the methylamine phosphate and the oxygen in the fruit samples in each step 5 is detected, and the results show the table 5. And the obtained forsythia suspense extract is put into the preparation process treatment of the Shuanghuanglian eye drops.

TABLE 5 residue of Methamidophos and omethoate from Forsythia suspensa extraction in Each step

The above example results demonstrate that methamidophos and omethoate remain after step 1 of forsythia suspensa extraction when 500g of forsythia suspensa in example 10 has 5.16 μ g of methamidophos and 7.79 μ g of omethoate, that is, when 10.32 μ g/kg of methamidophos and 15.58 μ g/kg of omethoate in forsythia suspensa. When the methamidophos content in 500g of forsythia suspensa in example 11 was 2.11 μ g and the omethoate content was 3.23 μ g, that is, when the methamidophos content in forsythia suspensa was 4.22 μ g/kg and the omethoate content was 6.46 μ g/kg, the methamidophos and omethoate were completely removed after the forsythia suspensa extraction step 1. Therefore, under the condition that the methamidophos residue of forsythia suspense in the forsythia suspense eye drops is controlled to be below 5 mu g/kg, such as below 4 mu g/kg, and the omethoate residue is controlled to be below 8 mu g/kg, such as below 6 mu g/kg, the methamidophos and the omethoate are completely removed after the forsythia suspense extraction step 1, and the forsythia suspense extract does not contain pesticide residue. Therefore, chlorogenic acid which is an effective component of honeysuckle cannot be influenced in the preparation.

Experimental example 4 influence of honeysuckle, forsythia and scutellaria baicalensis medicinal materials on effective components after removal of pesticide residues through supercritical pretreatment

The above experiments 1-3 can prove that whether the honeysuckle, the forsythia and the scutellaria baicalensis are adopted, one of the three medicinal materials has influence on the quality of the Shuanghuanglian eye drops as long as the medicinal material contains high residue methamidophos and omethoate. Therefore, one of the medicinal materials is selected to reduce the contents of methamidophos and omethoate by using a supercritical treatment technology, and whether the extracted medicinal material affects the content of chlorogenic acid which is an effective substance is examined. The results also represent the effect that other herbs can achieve using supercritical processing techniques.

The method comprises the steps of performing supercritical treatment on honeysuckle, fructus forsythiae and scutellaria baicalensis with high pesticide residue content by adopting a carbon dioxide supercritical treatment process, removing methamidophos and omethoate, respectively detecting the contents of methamidophos and omethoate and the content of chlorogenic acid, and extracting after the contents are qualified.

Example 12 using supercritical carbon dioxide to treat honeysuckle, the process comprises static extraction, dynamic extraction and two-stage resolution, static extraction, wherein the temperature of the dynamic extraction and the temperature of the two-stage resolution are both 30 ℃, the static extraction pressure is 10MPa, and the extraction time is 20 minutes; the dynamic extraction pressure is 25MPa, and the extraction time is 5 hours; the primary analysis pressure is 8MPa, the secondary analysis pressure is 5MPa, and the carbon dioxide flow is 1000L/h.

The honeysuckle extraction method and the detection method of chlorogenic acid, methamidophos and omethoate are the same as the examples in the test 1-1. Table 6 below represents the chlorogenic acid content of the lonicera japonica thunb without methamidophos and omethoate pesticide residues in each extraction step (example 1'), the chlorogenic acid content of the lonicera japonica thunb subjected to carbon dioxide supercritical treatment in each extraction step (example 12), and the chlorogenic acid content of the lonicera japonica thunb without carbon dioxide supercritical treatment and containing methamidophos and omethoate pesticide residues in each extraction step (example 3), respectively.

TABLE 6 influence of supercritical carbon dioxide treatment on chlorogenic acid content

The experiments prove that after the honeysuckle medicinal material is subjected to carbon dioxide supercritical treatment, the amount of methamidophos and omethoate pesticide residues can be effectively reduced, and the substantial influence on chlorogenic acid which is an effective substance in the honeysuckle medicinal material is not generated. After the medicinal material is subjected to supercritical extraction, the content of chlorogenic acid is obviously superior to that of the medicinal material which is not subjected to carbon dioxide supercritical treatment. Therefore, the pesticide residue can be effectively reduced by using the supercritical carbon dioxide treatment, and the effective substances in the extraction process of the medicinal materials cannot be influenced.

Experimental example 5 preparations were prepared by controlling pesticide residue and extraction of treated medicinal materials, respectively, and the influence of different treatments on chlorogenic acid content in eye drops was verified

Extracting flos Lonicerae with controlled content of methamidophos and omethoate or processed with supercritical carbon dioxide, fructus forsythiae and Scutellariae radix to obtain SHUANGHUANGLIAN eye drop, and checking chlorogenic acid content in the preparation. The results are given in Table 7 below:

TABLE 7 chlorogenic acid content in formulations using different treated herbs

The tests prove that under the condition of controlling the contents of methamidophos and omethoate in the medicinal materials, namely controlling the contents of methamidophos in the honeysuckle medicinal materials to be not more than 4 mug/kg and the contents of omethoate in the honeysuckle medicinal materials to be not more than 6 mug/kg, the equivalent chlorogenic acid content under the condition that neither methamidophos nor omethoate is detected can be obtained. Meanwhile, when methamidophos in the honeysuckle medicinal material is more than 4 mug/kg and omethoate is more than 6 mug/kg, the chlorogenic acid content equivalent to that under the condition that neither methamidophos nor omethoate is detected can be obtained after supercritical treatment. In addition, under the condition that methamidophos in honeysuckle medicinal materials is more than 4 mug/kg and omethoate is more than 6 mug/kg, the content of chlorogenic acid is reduced.

Therefore, the quality stability of the Shuanghuanglian eye drops can be improved by controlling the contents of methamidophos and omethoate in medicinal materials.

The above examples are only intended to illustrate the technical solution of the present invention and not to limit it; although the present invention has been described in detail with reference to preferred embodiments, it will be understood by those of ordinary skill in the art that: modifications to the specific embodiments of the invention or equivalent substitutions for parts of the technical features may be made; without departing from the spirit of the invention, it is intended to cover all modifications within the scope of the invention as claimed.

Claims

1. A method for improving the quality stability of Shuanghuanglian eye drops, which are prepared from extracts of honeysuckle, scutellaria and forsythia, comprises the following steps:

wherein, step 1) includes:

2. The method according to claim 1, wherein the methamidophos and omethoate content in the at least one crude drug to be extracted is controlled by the following steps:

-extracting if it is detected that the methamidophos content in the at least one drug substance to be extracted is not more than 5 μ g/kg, such as not more than 4 μ g/kg, for example not detected, and the omethoate content is not more than 8 μ g/kg, such as not more than 6 μ g/kg, for example not detected;

preferably, the first and second electrodes are formed of a metal,

-if it is detected that the methamidophos content in the at least one crude drug to be extracted is not more than 4 μ g/kg, for example not detected, and the omethoate content is not more than 6 μ g/kg, for example not detected, then the extraction is carried out;

3. The method according to claim 2, wherein the pesticide residue removal treatment is performed by carbon dioxide supercritical treatment.

4. The method according to any one of claims 1 to 3, wherein the at least one herb to be extracted comprises or is honeysuckle alone, forsythia suspensa alone, scutellaria baicalensis alone, a combination of honeysuckle and forsythia suspensa, a combination of honeysuckle and scutellaria baicalensis, a combination of forsythia suspensa and scutellaria baicalensis, or a combination of honeysuckle and forsythia suspensa and scutellaria baicalensis; preferably, the at least one medicinal material to be extracted comprises or is single honeysuckle, the combination of honeysuckle and forsythia, the combination of honeysuckle and scutellaria, or the combination of honeysuckle, forsythia and scutellaria; preferably, the at least one herb to be extracted comprises or is honeysuckle alone, and optionally, forsythia suspensa alone and/or scutellaria baicalensis alone.

5. The method according to any one of claims 1 to 4, wherein the at least one drug substance to be extracted comprises honeysuckle, such as honeysuckle alone, the method comprising:

-controlling the methamidophos content in the honeysuckle flower medicinal material to be extracted to be not more than 5 mug/kg, such as not more than 4 mug/kg, such as not detected, and the omethoate content to be not more than 8 mug/kg, such as not more than 6 mug/kg, such as not detected;

6. The method of claim 5, wherein

(i) The at least one medicinal material to be extracted further comprises forsythia suspense, such as forsythia suspense alone, and the method further comprises:

-extracting the forsythia suspense medicinal material to be extracted or extracting the forsythia suspense medicinal material to be extracted and the honeysuckle medicinal material to be extracted in a combining way to obtain an extract for preparing the Shuanghuanglian eye drops;

and/or

(ii) The at least one medicinal material to be extracted further comprises scutellaria baicalensis, such as scutellaria baicalensis alone, and the method further comprises:

7. A method for extracting an extract from medicinal materials for preparing Shuanghuanglian eye drops, which are prepared from extracts of honeysuckle, scutellaria and forsythia, comprises the following steps:

8. The method according to claim 7, wherein the methamidophos and omethoate content in the at least one crude drug to be extracted is controlled by:

preferably, the first and second electrodes are formed of a metal,

if the methamidophos content in the at least one medicinal material to be extracted is detected to be more than 4 mug/kg and/or the omethoate content is detected to be more than 6 mug/kg, pesticide residue removing treatment is firstly carried out until the methamidophos content is not more than 4 mug/kg, such as undetected state, and the omethoate content is not more than 6 mug/kg, such as undetected state, and then extraction is carried out;

preferably, the pesticide residue removal treatment is performed by carbon dioxide supercritical treatment;

preferably, the at least one herb to be extracted comprises or is honeysuckle alone, forsythia alone, scutellaria alone, a combination of honeysuckle and forsythia, a combination of honeysuckle and scutellaria, a combination of forsythia and scutellaria, or a combination of honeysuckle, forsythia and scutellaria; preferably, the at least one medicinal material to be extracted comprises or is the single honeysuckle, the combination of the honeysuckle and the forsythia, the combination of the honeysuckle and the scutellaria or the combination of the honeysuckle, the forsythia and the scutellaria; preferably, the at least one herb to be extracted comprises or is honeysuckle alone, and optionally, forsythia alone and/or scutellaria alone.

9. A preparation method of Shuanghuanglian eye drops, which is prepared from extracts of honeysuckle, scutellaria and forsythia, comprises the following steps:

1) Extracting flos Lonicerae, scutellariae radix and fructus forsythiae to obtain corresponding medicinal material extract;

wherein at least one selected from the group consisting of: honeysuckle extract, scutellaria extract, forsythia extract, or a combination thereof; preferably, the extract of honeysuckle, the extract of forsythia suspense, the extract of scutellaria baicalensis, the extract of a combination of honeysuckle and forsythia suspense, the extract of a combination of honeysuckle and scutellaria baicalensis, the extract of a combination of forsythia suspense and scutellaria baicalensis, and/or the extract of a combination of honeysuckle, forsythia suspense and scutellaria baicalensis; preferably, the extract of honeysuckle, the extract of the combination of honeysuckle and forsythia suspensa, the extract of the combination of honeysuckle and scutellaria baicalensis, and/or the extract of the combination of honeysuckle, forsythia suspensa and scutellaria baicalensis; preferably, the extract of honeysuckle flower, and/or the extract of the combination of honeysuckle flower and forsythia fruit.

10. An eye drop of Shuanghuanglian, which is prepared by the method of any one of claims 1 to 9.