Compound herba houttuyniae eye drops as well as preparation method and application thereof

Abstract

The invention relates to compound herba houttuyniae eye drops as well as a preparation method and application of the compound herba houttuyniae eye drops. Comprising the following preparation raw materials in percentage by mass: 1-6% of a herba houttuyniae extracting solution, 1-5% of an aglaia odorata extracting solution, 1-2% of a gelidium amansii extracting solution, 0.1-0.3% of acyclovir, 0.1-0.3% of tobramycin, 0.01-0.1% of dexamethasone sodium phosphate, 0.1-1% of sodium hyaluronate, 0.1-3% of glycerol and 88-93% of purified water. According to the compound herba houttuyniae eye drops prepared by the preparation method disclosed by the invention, the herba houttuyniae extracting solution, the aglaia odorata extracting solution, the gelidium amansii extracting solution, the acyclovir, the tobramycin and the dexamethasone sodium phosphate are combined for use, so that the compound herba houttuyniae eye drops have a relatively good curative effect on pets suffering from bacterium and virus mixed infection type conjunctivitis / keratitis; the compound herba houttuyniae eye drops are good in high-temperature-resistant storage stability and good in curative effect, the problem of frequent administration can be reduced, and the compound herba houttuyniae eye drops are more convenient to use and store.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of pet medicine, and particularly relates to a compound houttuynia cordata eye drop and a preparation method and application thereof. BACKGROUND

[0002] With the improvement of people's living standards, the status of pet family is increasingly promoted, and more and more pets have become an indispensable member in many families, and pet health naturally becomes the focus of attention. Pets get sick, and eye diseases are one of the most common diseases, which are mostly caused by external stimulation such as trauma, or bacterial, viral or mycoplasma infection. Because the blood vessels and lymphatic tissues of the conjunctiva are rich, the antigen of the body and the outside world is easy to sensitize it, which shows that the eyes are red, itchy, have eye discharge, scratch the eyes and tears, and the Chinese medicine is called 'Tianxing Chimei', commonly known as'red eye disease'.

[0003] Among them, bacterial conjunctivitis is mostly caused by Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa or Staphylococcus epidermidis infection; viral conjunctivitis is mostly caused by Herpes Simplex virus infection; at present, single component eye drops such as tobramycin or acyclovir single component drugs are often used for treatment in clinic, but single component drugs cannot meet the treatment requirements of bacterial and viral mixed infection. If multiple single component drugs are used for combined treatment, each single component drug needs to be administered each time, the administration operation is frequent, the drug is highly irritating, the retention time is short, the curative effect is poor, and the use is very inconvenient. Based on this, the application provides a compound houttuynia cordata eye drop and a preparation method and application thereof to solve the above technical problems. SUMMARY

[0004] The application aims to solve the above problems and provide a compound houttuynia cordata eye drop and a preparation method and application thereof.

[0005] The application achieves the above-mentioned purpose through the following technical solutions: The application provides a compound houttuynia cordata eye drop, which comprises the following preparation raw materials in mass percentage: houttuynia cordata extract 1-6%, micranthium extract 1-5%, gelidium amansii extract 0.5-2%, acyclovir 0.1-0.3%, tobramycin 0.1-0.3%, dexamethasone sodium phosphate 0.01-0.1%, sodium hyaluronate 0.1-1%, glycerol 0.1-3%, and purified water 88-93%.

[0006] As a further optimization scheme of the present application, the compound Houttuynia cordata eye drops comprises the following raw materials by mass percentage: Houttuynia cordata extract 3%, Rhizotomy extract 2%, Gelidium amansii extract 1%, acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerol 0.5%, purified water 92.575%.

[0007] As a further optimization scheme of the present application, the method for obtaining the Houttuynia cordata extract / Rhizotomy extract / Gelidium amansii extract comprises the following steps: soaking the screened, washed and dried Houttuynia cordata raw material / Rhizotomy raw material / Gelidium amansii raw material in purified water, adjusting the pH to 5.0-6.0, ultrasonic-assisted extraction at 40-50℃ for 1-2h, and obtaining the Houttuynia cordata extract / Rhizotomy extract / Gelidium amansii extract through membrane filtration of the obtained mixed solution. The Houttuynia cordata raw material is the stems and leaves of Houttuynia cordata in a mass ratio of 1:2-3. The Rhizotomy raw material is the leaves of Rhizotomy.

[0008] As a further optimization scheme of the present application, the ultrasonic-assisted extraction is performed at a power of 350-450W, a frequency of 45-65kHz, a temperature of 60℃-70℃, and a time of 25-40min, with 30s of ultrasonic treatment and 10s of pause, and the cycle is repeated.

[0009] As a further optimization scheme of the present application, the membrane filtration is specifically performed by adjusting the pH to 5-6, and performing membrane filtration under the condition of 0.1-0.5MPa by using an ultrafiltration membrane with a molecular weight cut-off of 10kDa.

[0010] As a further optimization scheme of the present application, the method for obtaining the Houttuynia cordata extract / Rhizotomy extract / Gelidium amansii extract further comprises the following steps: after the membrane filtration, the membrane filtration filtrate is prepared into an aqueous solution with a mass concentration of 50-70mg / mL, papain and / or alkaline protease are added, the total amount of the added protease is 0.01-1g / kg Houttuynia cordata extract / Rhizotomy extract / Gelidium amansii extract, the pH is adjusted to 7-9, and the hydrolysis is performed at a temperature of 50-60℃ for 2-3h, and then inactivated, and the mixture is left to room temperature, centrifuged at 5000-8000r / min for 8-15min, and the supernatant is separated to obtain the Houttuynia cordata extract / Rhizotomy extract / Gelidium amansii extract.

[0011] The present application also provides a preparation method of the compound Houttuynia cordata eye drops, and the specific steps are as follows: uniformly mixing the Houttuynia cordata extract, Rhizotomy extract, Gelidium amansii extract, acyclovir, tobramycin and dexamethasone sodium phosphate in a proper proportion, adding the Gelidium amansii extract, sodium hyaluronate, glycerol and purified water, fully mixing, sterilizing and filtering, filling into eye drop bottles and sealing for storage.

[0012] As a further optimization of the present invention, the eye drop bottle is an eye drop bottle body made of low-density polyethylene resin and an eye drop bottle cap made of polypropylene.

[0013] Application of a compound houttuynia cordata eye drops in the preparation of treatments or improvements for pet eye diseases.

[0014] As a further optimization of the present invention, the eye disease includes bacterial and viral mixed infection type conjunctivitis / keratitis, and the external dosage of the compound houttuynia cordata eye drops is 2-5 times a day, with each dose being 0.05-0.5g / kg.

[0015] The beneficial effects of this invention are as follows: The compound houttuynia cordata eye drops prepared by this invention combine houttuynia cordata extract, Michelia alba extract, and Agaricus esculentus extract with acyclovir, tobramycin, and dexamethasone sodium phosphate. It has a good therapeutic effect on pets suffering from mixed bacterial and viral conjunctivitis / keratitis. The compound houttuynia cordata eye drops have good high-temperature storage stability, good efficacy, and can reduce the problem of frequent administration, making it more convenient to use and store. Detailed Implementation

[0016] The present application will now be described in further detail. It should be noted that the following specific embodiments are only used to further illustrate the present application and should not be construed as limiting the scope of protection of the present application. Those skilled in the art can make some non-essential improvements and adjustments to the present application based on the above application content.

[0017] I. Materials 1. pH adjusters: citric acid, sodium hydroxide; 2. Papain: Purchased from Hefei Hongrui Biotechnology Co., Ltd., with a purity of 99% and an enzyme activity of 7.5 × 10⁻⁶. 5 U / g; 3. Alkaline protease: Purchased from Shanghai Koraman Reagent Co., Ltd., purity 99%, enzyme activity 7.2 × 10⁻⁶. 5 U / g.

[0018] 4. Raw material of Houttuynia cordata: It is made by mixing the stems and leaves of Houttuynia cordata Thunb. in a mass ratio of 1:2-3. The stems and leaves of Houttuynia cordata used in the following experiments were mixed in a mass ratio of 1:2.5. 5. Raw material for Aglaia odorata Lour.: Leaves of Aglaia odorata Lour.; 6. Raw material for agar-agar: The whole agar-agar (Gelidium amansii (Lamouroux Lamouroux, 1813)) is used.

[0019] Unless otherwise specified, the methods used in this invention are conventional methods known to those skilled in the art, and the raw materials and reagents used are commercially available products.

[0020] II. Methods Example 1 In this embodiment, the preparation method of compound houttuynia cordata eye drops for treating or improving pet eye diseases is as follows: (1) Preparation of Houttuynia cordata extract, Michelia alba extract and Agaricus esculentus extract 1.1 Soak the screened, cleaned and dried Houttuynia cordata / Mizilan / Agaricus esculentus raw materials in purified water, adjust the pH to 5.4, soak at 45℃ for 1.5h, and then perform ultrasonic-assisted extraction. The ultrasonic-assisted extraction power is 420W, the frequency is 55kHz, the temperature is 65℃, the time is 25-40min, the ultrasonic treatment is 30s, the pause is 10s, and this cycle is repeated. 1.2 The mixture obtained in step 1.1 above is filtered through a membrane to obtain Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract. Specifically, the membrane filtration is performed by adjusting the pH to 5.5 and filtering with an ultrafiltration membrane with a molecular weight cutoff of 10 kDa at 3.5 MPa to obtain the filtrate, which is used as the Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract.

[0021] (2) Preparation of compound houttuynia cordata eye drops In this embodiment, the compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: houttuynia cordata extract 6%, Michelia alba extract 1%, Agaricus esculentus extract 2%, acyclovir 0.1%, tobramycin 0.1%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.7%, glycerin 0.6%, and purified water 89.475%.

[0022] The specific steps of the preparation method are as follows: Houttuynia cordata extract, Michelia alba extract, and Agaricus oleraceus extract are mixed evenly with acyclovir, tobramycin, and dexamethasone sodium phosphate in a certain proportion. Then, Agaricus oleraceus extract, sodium hyaluronate, glycerin, and purified water are added, and the mixture is thoroughly mixed, sterilized, filtered, and filled into eye drop bottles for sealing and storage (the eye drop bottle is an eye drop bottle body made of low-density polyethylene resin or polyethylene terephthalate and an eye drop bottle cap made of polypropylene).

[0023] Example 2 In this embodiment, the preparation method of compound houttuynia cordata eye drops for treating or improving pet eye diseases is as follows: (1) Preparation of Houttuynia cordata extract, Michelia alba extract and Agaricus esculentus extract 1.1 Soak the screened, cleaned and dried Houttuynia cordata / Mizilan / Agaricus esculentus raw materials in purified water, adjust the pH to 5.4, soak at 45℃ for 1.5h, and then perform ultrasonic-assisted extraction. The ultrasonic-assisted extraction power is 420W, the frequency is 55kHz, the temperature is 65℃, the time is 25-40min, the ultrasonic treatment is 30s, the pause is 10s, and this cycle is repeated. 1.2 The mixture obtained in step 1.1 above is filtered through a membrane to obtain Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract. Specifically, the membrane filtration is performed by adjusting the pH to 5.5 and filtering with an ultrafiltration membrane with a molecular weight cutoff of 10 kDa at 3.5 MPa to obtain the filtrate, which is used as the Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract.

[0024] (2) Preparation of compound houttuynia cordata eye drops In this embodiment, the compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: houttuynia cordata extract 3%, Michelia alba extract 2%, Agaricus esculentus extract 1%, acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerin 0.5%, and purified water 92.575%.

[0025] The specific steps of the preparation method are as follows: Houttuynia cordata extract, Michelia alba extract, and Agaricus oleraceus extract are mixed evenly with acyclovir, tobramycin, and dexamethasone sodium phosphate in a certain proportion. Then, Agaricus oleraceus extract, sodium hyaluronate, glycerin, and purified water are added, and the mixture is thoroughly mixed, sterilized, filtered, and filled into eye drop bottles for sealing and storage (the eye drop bottle is an eye drop bottle body made of low-density polyethylene resin or polyethylene terephthalate and an eye drop bottle cap made of polypropylene).

[0026] Example 3 In this embodiment, the preparation method of compound houttuynia cordata eye drops for treating or improving pet eye diseases is as follows: (1) Preparation of Houttuynia cordata extract, Michelia alba extract and Agaricus esculentus extract 1.1 Soak the screened, cleaned and dried Houttuynia cordata / Mizilan / Agaricus esculentus raw materials in purified water, adjust the pH to 5.4, soak at 45℃ for 1.5h, and then perform ultrasonic-assisted extraction. The ultrasonic-assisted extraction power is 420W, the frequency is 55kHz, the temperature is 65℃, the time is 25-40min, the ultrasonic treatment is 30s, the pause is 10s, and this cycle is repeated. 1.2 The mixture obtained in step 1.1 above is filtered through a membrane to obtain Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract. Specifically, the membrane filtration is performed by adjusting the pH to 5.5 and filtering with an ultrafiltration membrane with a molecular weight cutoff of 10 kDa at 3.5 MPa to obtain the filtrate, which is used as the Houttuynia cordata extract / Miscanthus sinensis extract / Agaricus jelly extract.

[0027] (2) Preparation of compound houttuynia cordata eye drops In this embodiment, the compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: houttuynia cordata extract 1%, Michelia alba extract 5%, Agaricus esculentus extract 1.5%, acyclovir 0.1%, tobramycin 0.15%, dexamethasone sodium phosphate 0.055%, sodium hyaluronate 0.5%, glycerin 0.8%, and purified water 90.895%.

[0028] The specific steps of the preparation method are as follows: Houttuynia cordata extract, Michelia alba extract, and Agaricus oleraceus extract are mixed evenly with acyclovir, tobramycin, and dexamethasone sodium phosphate in a certain proportion. Then, Agaricus oleraceus extract, sodium hyaluronate, glycerin, and purified water are added, and the mixture is thoroughly mixed, sterilized, filtered, and filled into eye drop bottles for sealing and storage (the eye drop bottle is an eye drop bottle body made of low-density polyethylene resin or polyethylene terephthalate and an eye drop bottle cap made of polypropylene).

[0029] Example 4 In this embodiment, the preparation method of the compound houttuynia cordata eye drops for treating or improving pet eye diseases is as follows: (1) Preparation of Houttuynia cordata extract, Michelia alba extract and Agaricus esculentus extract 1.1 Soak the screened, cleaned and dried Houttuynia cordata / Mizilan / Agaricus esculentus raw materials in purified water, adjust the pH to 5.4, soak at 45℃ for 1.5h, and then perform ultrasonic-assisted extraction. The ultrasonic-assisted extraction power is 420W, the frequency is 55kHz, the temperature is 65℃, the time is 25-40min, the ultrasonic treatment is 30s, the pause is 10s, and this cycle is repeated. 1.2 The mixture obtained in step 1.1 above is filtered through a membrane to obtain Houttuynia cordata extract / Mizilan extract / Agaricus edulis extract. Specifically, the membrane filtration is performed by adjusting the pH to 5.5 and filtering with an ultrafiltration membrane with a molecular weight cutoff of 10 kDa at 3.5 MPa to obtain the filtrate. 1.3 Prepare an aqueous solution with a mass concentration of 65 mg / mL from the filtrate obtained in step 1.2 above, add papain (total protease added at a rate of 0.8 g / kg of Houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract), adjust the pH to 7.5, hydrolyze at 56℃ for 2.5 h, inactivate the protease, let it stand at room temperature, centrifuge at 6000 r / min for 10 min, and separate the supernatant to obtain Houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract.

[0030] (2) Preparation of compound houttuynia cordata eye drops In this embodiment, the compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: houttuynia cordata extract 3%, Michelia alba extract 2%, Agaricus esculentus extract 1%, acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerin 0.5%, and purified water 92.575%.

[0031] The specific steps of the preparation method are as follows: Houttuynia cordata extract, Michelia alba extract, and Agaricus oleraceus extract are mixed evenly with acyclovir, tobramycin, and dexamethasone sodium phosphate in a certain proportion. Then, Agaricus oleraceus extract, sodium hyaluronate, glycerin, and purified water are added, and the mixture is thoroughly mixed, sterilized, filtered, and filled into eye drop bottles for sealing and storage (the eye drop bottle is an eye drop bottle body made of low-density polyethylene resin or polyethylene terephthalate and an eye drop bottle cap made of polypropylene).

[0032] Example 5 In this embodiment, based on Example 4, the enzyme reagent used in step 1.3 of step (1) of the preparation method of compound houttuynia cordata eye drops for treating or improving pet eye diseases was adjusted. After adjustment, the obtained filtrate was prepared into an aqueous solution with a mass concentration of 65 mg / mL, and alkaline protease (total protease added amount of 0.8 g / kg houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract) was added. The pH was adjusted to 7.5, and after hydrolysis at 56°C for 2.5 h, after inactivation treatment, it was allowed to stand at room temperature, centrifuged at 6000 r / min for 10 min, and the supernatant was separated to obtain houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract. Everything else is the same as in Example 4.

[0033] Example 6 In this embodiment, based on Example 4, the enzyme reagent used in step 1.3 of step (1) of the preparation method of compound houttuynia cordata eye drops for treating or improving pet eye diseases was adjusted. After adjustment, the obtained filtrate was prepared into an aqueous solution with a mass concentration of 65 mg / mL, and papain and alkaline protease with a mass ratio of 1:1 were added (the total amount of protease added was 0.8 g / kg houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract), the pH was adjusted to 7.5, and after hydrolysis at 56°C for 2.5 h, after inactivation treatment, it was allowed to stand at room temperature, centrifuged at 6000 r / min for 10 min, and the supernatant was separated to obtain houttuynia cordata extract / Miscanthus sinensis extract / Glechoma hederacea extract; Everything else is the same as in Example 4.

[0034] Comparative Example 1 In this comparative example, the raw materials for preparing the compound houttuynia cordata eye drops used to treat or improve pet eye diseases were adjusted, with purified water replacing the extract of *Gynostemma pentaphyllum*. The adjusted compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: 3% houttuynia cordata extract, 1% *Gynostemma pentaphyllum* extract, 0.2% acyclovir, 0.2% tobramycin, 0.025% dexamethasone sodium phosphate, 0.5% sodium hyaluronate, 0.5% glycerin, and 94.575% purified water. Everything else is consistent with Example 6.

[0035] Comparative Example 2 In this comparative example, the raw materials for preparing compound houttuynia cordata eye drops for treating or improving pet eye diseases were adjusted, with purified water replacing agaric extract. The adjusted compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: houttuynia cordata extract 3%, agaric extract 2%, acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerin 0.5%, and purified water 93.575%. Everything else is consistent with Example 6.

[0036] Comparative Example 3 In this comparative example, the raw materials for preparing the compound houttuynia cordata eye drops used to treat or improve pet eye diseases were adjusted. Purified water was used to replace the extracts of *Gynostemma pentaphyllum* and *Agaricus esculentus*. After adjustment, the compound houttuynia cordata eye drops comprise the following raw materials by mass percentage: 3% houttuynia cordata extract, 0.2% acyclovir, 0.2% tobramycin, 0.025% dexamethasone sodium phosphate, 0.5% sodium hyaluronate, 0.5% glycerin, and 95.575% purified water. Everything else is consistent with Example 6.

[0037] Comparative Example 4 In this comparative example, the raw materials for preparing compound houttuynia cordata eye drops for treating or improving pet eye diseases were adjusted, with purified water replacing houttuynia cordata extract. The adjusted compound eye drops comprise the following raw materials by mass percentage: 2% *Gynostemma pentaphyllum* extract, 1% *Gynostemma pentaphyllum* extract, 0.2% acyclovir, 0.2% tobramycin, 0.025% dexamethasone sodium phosphate, 0.5% sodium hyaluronate, 0.5% glycerin, and 95.575% purified water. Everything else is consistent with Example 6.

[0038] Blank group In this blank group, the raw materials for preparing compound houttuynia cordata eye drops for treating or improving pet eye diseases were adjusted by replacing houttuynia cordata extract, Michelia alba extract, and Agaricus edulis extract with purified water. After adjustment, the compound eye drops comprise the following raw materials by mass percentage: acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerin 0.5%, and purified water 98.575%. Everything else is consistent with Example 6.

[0039] III. Experiment (1) Anti-inflammatory performance test Drugs subjected to high-temperature storage: eye drop bottles made of low-density polyethylene resin (room temperature group A, room temperature group A) or polyethylene terephthalate PET (high temperature group B, high temperature group B) and eye drop bottle caps made of polypropylene were used to store the compound houttuynia cordata eye drops / compound eye drops prepared in Examples 1-6, Comparative Examples 1-4 and the blank group, and were kept at a high temperature of 65°C for 90 days.

[0040] Drugs stored at room temperature: eye drop bottles made of low-density polyethylene resin (room temperature group A, room temperature group A) or PET (high temperature group B, high temperature group B) and eye drop bottle caps made of polypropylene were used to store the compound houttuynia cordata eye drops prepared in Examples 1-6, Comparative Examples 1-4 and the blank group at a high temperature of 25°C for 90 days.

[0041] Experimental Methods: Rabbits (New Zealand rabbits) weighing 2-2.5 kg were selected and randomly divided into 13 groups (Examples 1-6, Comparative Examples 1-4, Blank Group, Negative Control Group, and Positive Control Group). After anesthetizing the rabbits, three 1 mm incisions were made on the cornea of ​​the rabbits in Examples 1-6, Comparative Examples 1-4, Blank Group, and Positive Control Group using a sterile 25-gauge needle, and instilled with 4.8 × 10⁻⁶ ppm of ointment. 6A successful Pseudomonas aeruginosa and herpes simplex virus mixed infection model can be determined by the presence of obvious conjunctival hyperemia, purulent discharge and corneal opacity 24 hours after infection, with 10 μL of bacterial solution containing 10 μL of CFU Pseudomonas aeruginosa (such as ATCC 19660) and 10 μL of viral solution containing 4.3×106 CFU of herpes simplex virus (such as HSV-1 KOS). Six hours after successful model construction, the rabbits in Examples 1-6, Comparative Examples 1-4, and the blank group were given medication (instilled into the eyes three times a day, each dose being 0.05-0.5 g / kg; 0.2 g / kg was used in this experiment). The negative control group and the positive control group were given an equal volume of physiological saline eye drops (the storage bottle, cap, and storage method were the same as those in Examples 1-6, Comparative Examples 1-4, and the blank group). The treatment lasted for 10 days, and the serum levels of inflammatory factors (IL-1β, IL-6) (pg / mL) were measured, as shown in Table 1. Table 1. Statistical analysis of efficacy test data for compound houttuynia cordata eye drops after high-temperature and room-temperature storage treatment. ; Experimental Conclusion: Based on the data analysis in Table 1, it can be seen that the efficacy of Houttuynia cordata extract combined with acyclovir, tobramycin, and dexamethasone sodium phosphate in treating pets is better than that of using them alone. Furthermore, the combination of Houttuynia cordata extract, Aster tataricus extract, and Gracilaria extract can significantly improve the therapeutic effect and make the compound Houttuynia cordata eye drops have high-temperature storage stability (the eye drop bottle is made of low-density polyethylene resin and the eye drop bottle cap is made of polypropylene), making it more convenient to use and store, and resulting in better therapeutic effects.

[0042] (2) Clinical trials of drug efficacy Experimental subjects: 330 dogs and cats with bacterial and viral conjunctivitis in their eyes at a pet hospital.

[0043] Experimental procedure: The sick pets were randomly divided into 11 groups of 30 each and administered the drug.

[0044] The administration method was intravitreal instillation into the eyes, three times a day, with a dosage of 0.05-0.5 g / kg each time. In this application experiment, 0.2 g / kg was used for 7 consecutive days. During this period, observations were also conducted. No adverse reactions such as eyelid spasm, stinging, tearing, conjunctival congestion, periorbital hair loss, mild redness and swelling, itching, eyelid protrusion, rapid breathing, drooling, vomiting, or unsteady gait were observed in any of the pets in all groups.

[0045] Experimental Results Statistics: ① Efficacy Rate: During the experiment, pets with significant improvement in clinical symptoms and near-normal eye condition were considered effective, and the efficacy rate was calculated accordingly. ② Cure Rate: During the experiment, pets with lively spirits and normal eye condition after medication were considered cured, and the cure rate was calculated accordingly. ③ Compliance Rate: Calculated based on drug compliance and post-administration resistance in pets. All results are statistically presented in Table 2 below. Table 2. Statistical analysis of efficacy test data for compound houttuynia cordata eye drops stored at room temperature. ; Experimental Conclusion: Based on the data analysis in Table 2, it can be seen that the compound houttuynia cordata eye drops in Example 6 of this application have better therapeutic effects. This indicates that houttuynia cordata, celery, and agar-agar have better efficacy after enzymatic hydrolysis. Moreover, the combination of the three has a certain synergistic effect, which can significantly improve the efficacy. When used in combination with acyclovir, tobramycin, and dexamethasone sodium phosphate, it has a good effect on pets with mixed bacterial and viral conjunctivitis / keratitis. It has good high-temperature storage stability, good efficacy, and can reduce the problem of frequent administration, making it more convenient to use and store.

[0046] The experiments described above only illustrate several embodiments of the present invention, and while the descriptions are relatively specific and detailed, they should not be construed as limiting the scope of the present invention. It should be noted that those skilled in the art can make various modifications and improvements without departing from the concept of the present invention, and these modifications and improvements all fall within the scope of protection of the present invention.

Claims

1. A compound Houttuynia cordata eye drop, characterized in that: The compound Houttuynia cordata eye drops include the following mass percentages of raw materials: Houttuynia cordata extract 1-6%, Rhynchosia volubilis extract 1-5%, Gelidium amansii extract 0.5-2%, acyclovir 0.1-0.3%, tobramycin 0.1-0.3%, dexamethasone sodium phosphate 0.01-0.1%, sodium hyaluronate 0.1-1%, glycerol 0.1-3%, and purified water 88-93%. ​ 2. The compound Houttuynia cordata eye drop of claim 1, characterized in that: The compound Houttuynia cordata eye drops include the following mass percentages of raw materials: Houttuynia cordata extract 3%, Rhynchosia volubilis extract 2%, Gelidium amansii extract 1%, acyclovir 0.2%, tobramycin 0.2%, dexamethasone sodium phosphate 0.025%, sodium hyaluronate 0.5%, glycerol 0.5%, and purified water 92.575%.

3. The compound Houttuynia cordata eye drop of claim 2, characterized in that: The method for obtaining the Houttuynia cordata extract / Rhynchosia volubilis extract / Gelidium amansii extract is as follows: the screened, washed and dried Houttuynia cordata raw material / Rhynchosia volubilis raw material / Gelidium amansii raw material is soaked in purified water, the pH is adjusted to 5.0-6.0, ultrasonic-assisted extraction is carried out after soaking at 40-50 DEG C for 1-2 h, and the obtained mixed solution is subjected to membrane filtration to obtain the Houttuynia cordata extract / Rhynchosia volubilis extract / Gelidium amansii extract; The Houttuynia cordata raw material is the stems and leaves of Houttuynia cordata compounded at a mass ratio of 1:2-3; The Rhynchosia volubilis raw material is the leaves of Rhynchosia volubilis; The Gelidium amansii raw material is the whole Gelidium amansii.

4. The compound Houttuynia cordata eye drop of claim 3, characterized in that: The ultrasonic-assisted extraction is carried out at a power of 350-450 W, a frequency of 45-65 kHz, a temperature of 60-70 DEG C, and a time of 25-40 min, and the ultrasonic treatment is carried out for 30 s, paused for 10 s, and then the cycle is repeated.

5. The compound Houttuynia cordata eye drop of claim 3, characterized in that: The membrane filtration is specifically as follows: the pH is adjusted to 5-6, and the membrane filtration is carried out under the condition of 0.1-0.5 MPa by using an ultrafiltration membrane with a molecular weight cut-off of 10 kDa.

6. The compound Houttuynia cordata eye drop of claim 3, characterized in that: The method for obtaining the Houttuynia cordata extract / Rhynchosia volubilis extract / Gelidium amansii extract further includes the following steps: after the membrane filtration, the membrane filtration filtrate is prepared into an aqueous solution with a mass concentration of 50-70 mg / mL, papain and / or alkaline protease are added, the total addition amount of the protease is 0.01-1 g / kg Houttuynia cordata extract / Rhynchosia volubilis extract / Gelidium amansii extract, the pH is adjusted to 7-9, hydrolysis is carried out at a temperature of 50-60 DEG C for 2-3 h, inactivation treatment is carried out, and then the system is left to stand until room temperature, centrifugation is carried out at 5000-8000 r / min for 8-15 min, and the supernatant is separated to obtain the Houttuynia cordata extract / Rhynchosia volubilis extract / Gelidium amansii extract.

7. The preparation method of the compound Houttuynia cordata eye drops according to any one of claims 1-6, characterized in that: The specific steps are as follows: the Houttuynia cordata extract, Rhynchosia volubilis extract and Gelidium amansii extract are uniformly mixed with acyclovir, tobramycin and dexamethasone sodium phosphate according to the proportion, the Gelidium amansii extract, sodium hyaluronate, glycerol and purified water are added, and then the mixture is fully mixed, sterilized and filtered, filled into eye drop bottles and sealed for storage.

8. The preparation method of the compound Houttuynia cordata eye drops according to claim 7, characterized in that: The eye drop bottle is an eye drop bottle body made of low-density polyethylene resin and an eye drop bottle cap made of polypropylene.

9. The compound Houttuynia cordata eye drops according to any one of claims 1-6 for use in the treatment or improvement of pet eye diseases.

10. Use according to claim 9, characterized in that: The eye diseases include bacterial, viral mixed infection conjunctivitis / corneal inflammation, the external use dosage of the compound fishy grass eye drop is 0.05-0.5g / kg, 2-5 times a day.