CN111494452A - Eye medicine and its preparing method - Google Patents
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Abstract
The invention discloses an ophthalmic medicament and a preparation method thereof. The ophthalmic preparation comprises an extract of emblic leafflower fruit and water for injection. The eye medicament can provide a protective effect on viruses which can be infected by eyes, and experimental research shows that the eye medicament has high-efficiency broad-spectrum antiviral activity, particularly has obvious treatment effect on new coronavirus and influenza virus, can effectively inhibit the infection and the transmission of the viruses, and has good prevention and control significance on the transmission of diseases caused by the infection of the viruses on human bodies. Moreover, the main effective components of the eye medicament are derived from natural plants, and the eye medicament has the advantages of being natural, safe, mild in medicinal effect and the like, and is simple in preparation method, low in cost and good in application prospect.
Description
Technical Field
The invention belongs to the technical field of medicines. More particularly, it relates to an ophthalmic drug and a method for preparing the same.
Background
The eye is one of the major routes of viral infection, and the body may be infected by direct or indirect contact with the eye, including splashes (e.g., blood splashes, splash while intubating, etc.) and droplet transmission (sneezing or coughing), contact transmission (e.g., rubbing the eye with hands), fecal-to-eye transmission, nasal-to-eye transmission, mouth-to-eye transmission (through contaminated hands or objects), and transmission of ocular secretions and tears.
Currently, there are a lot of studies on antiviral ophthalmic formulations, but the therapeutic effect is limited, and often only limited symptoms caused by several viruses are available without broad spectrum, for example, clinical studies show that povidone-iodine eye drops have only limited efficacy, and cause additional irritation in inflamed eyes, sometimes even conjunctival discoloration; patent CN201580005116.7 discloses a composition effective against viral conjunctivitis, using iota-carrageenan as an antiviral active ingredient, only for the treatment of viral eye infections caused by adenovirus of subtype D or influenza a virus of subtype H7. Particularly, a novel coronavirus (SARS-CoV-2) causing pneumonia epidemic caused by global outbreak at the end of 2019 can rapidly progress and even die, has extremely high lethality and great harm, but at present, no effective treatment method for viral conjunctivitis caused by SARS-CoV-2 infection exists, and unified treatment standards are lacked.
Therefore, there is a need to develop a complete and effective antiviral drug for eyes with a wide application range to prevent the eyes from being infected by viruses.
Disclosure of Invention
The technical problem to be solved by the invention is to overcome the defects and shortcomings of the prior art and provide an efficient broad-spectrum ophthalmic antiviral composition, an ophthalmic medicament and a preparation method thereof.
The invention aims to provide an ophthalmic antiviral composition.
The second object of the present invention is to provide the use of said composition for the preparation of an antiviral ophthalmic agent.
The third purpose of the invention is to provide a preparation method of the ophthalmic antiviral agent.
The above purpose of the invention is realized by the following technical scheme:
the invention utilizes the emblic leafflower fruit extract as an active substance to prepare the antiviral composition for eyes, and researches show that the emblic leafflower fruit extract has a remarkable inhibiting effect on various viruses entering eyes. Therefore, the present invention prepares an ophthalmic antiviral preparation using the extract of emblica officinalis as an active material.
Further, the virus is varicella-zoster virus (VZV), Cytomegalovirus (cytomegavirus), Adenovirus (Adenovirus), Zika virus (ZIKV), lassa virus (L asa virus, L ASV), Ebola Virus Disease (EVD), dengue virus (DENV), HT L V-1(Human T-cell leukavirus type 1), Coronavirus (Coronavirus, CoV), Influenza virus (Influenza virus, IV).
Wherein the coronavirus is SARS-CoV-2, SARS-CoV, MERS-CoV, HCoV-229E, HCoV-N L63, HCoV-OC43, HCoV-HKU 1;
the influenza virus is influenza A virus, influenza B virus and influenza C virus; the influenza A virus is H1N1, H2N3, H5N1 and H7N9, and the influenza B virus is a Yamagata system.
Based on the above, the invention provides an ophthalmic antiviral composition, which comprises an extract of emblic leafflower fruit and water for injection.
Preferably, the emblic extract is an aqueous extract of emblic.
As a preferred embodiment of the present invention, the present invention provides a method for preparing an aqueous extract of emblic leafflower fruit: extracting fructus Phyllanthi powder with deionized water 2-12 times of the weight of fructus Phyllanthi powder for 2-6 hr, recovering water extract, and concentrating to obtain fructus Phyllanthi water extract.
Fructus Phyllanthi is mature dry fruit of Phyllanthus emblica of Phyllanthus of Euphorbiaceae. The emblic leafflower fruit is sour and slightly astringent in taste, capable of clearing heat and cooling blood, helping digestion and strengthening spleen, and helping produce saliva and slake thirst, and mainly treats blood heat and blood stasis, dyspepsia, abdominal distension, cough, laryngalgia, dry mouth and vitamin C deficiency. In Tibetan medicine, emblic leafflower fruit is mainly used for treating bacon disease, red-bar disease, blood disease, hypertension and the like, and modern research results show that the emblic leafflower fruit also has the effects of resisting inflammation, resisting oxidation, resisting aging, protecting liver and the like. The experimental research results show that the phyllanthus emblica extract is used as the active substance to prepare the ophthalmic medicament, and the ophthalmic medicament has obvious inhibitory action on various viruses, especially on various coronavirus and influenza viruses, so that the ophthalmic medicament has good broad-spectrum antiviral action.
Preferably, the ophthalmic antiviral composition further comprises an osmotic pressure regulator, an antioxidant, a solubilizer, a bacteriostatic agent and a tackifier.
Preferably, in the ophthalmic antiviral composition, each 1L composition comprises, by weight, 8-20 parts of emblic leafflower fruit extract, 3-5 parts of osmotic pressure regulator, 0.1-5 parts of antioxidant, 0.5-10 parts of solubilizer, 0.1-0.5 part of bacteriostatic agent, 0.1-5 parts of tackifier, 0.1-0.5 part of borneol and the balance of water for injection.
Preferably, each 1L composition comprises fructus Phyllanthi extract 10-18 parts, osmotic pressure regulator 4-5 parts, antioxidant 0.5-3 parts, solubilizer 2-6 parts, bacteriostatic agent 0.1-0.3 part, tackifier 1-3 parts, Borneolum 0.2-0.3 part, and water for injection in balance.
Furthermore, preferably, each 1L composition comprises fructus Phyllanthi extract 18 parts, osmotic pressure regulator 4 parts, antioxidant 2 parts, solubilizer 3 parts, bacteriostatic agent 0.2 parts, tackifier 2 parts, Borneolum 0.3 parts, and water for injection in balance.
Preferably, the ophthalmic antiviral composition further comprises a metal salt.
More preferably, the metal salt is one or more of zinc salt, iron salt, calcium salt, magnesium salt, tungsten salt and rubidium salt.
More preferably, the metal salt is one or more of zinc sulfate, zinc gluconate, ferrous gluconate, calcium gluconate, magnesium oxide, sodium tungstate and rubidium iodide.
The invention utilizes metal salt such as zinc sulfate, calcium gluconate, zinc gluconate and the like to ionize in body fluid to obtain metal cations, and the metal cations have synergistic effect with the emblic leafflower fruit extract, so that the virus can be further inhibited, and the antiviral curative effect is obviously improved.
Preferably, in the antiviral composition for eyes, each 1L composition comprises, by weight, 8-20 parts of emblic leafflower fruit extract, 3-5 parts of osmotic pressure regulator, 0.1-5 parts of antioxidant, 0.5-10 parts of solubilizer, 0.1-0.5 part of bacteriostatic agent, 0.1-5 parts of tackifier, 0.1-0.5 part of borneol, 2-20 parts of metal salt and the balance of water for injection, wherein, preferably, the metal salt is 4-15 parts, more preferably 8 parts.
Further, preferably, the osmolality adjusting agent includes, but is not limited to, sodium chloride or boric acid; the antioxidant comprises one or more of sodium bisulfite, sodium sulfite, sodium thiosulfate, sodium metabisulfite and vitamin C; the solubilizer includes but is not limited to tween-80 or tween-20; such bacteriostatic agents include, but are not limited to, benzalkonium chloride or benzalkonium bromide; the tackifier comprises one or more of sodium hyaluronate, hydroxypropyl methylcellulose, povidone and polyvinyl alcohol.
The invention also provides application of the ophthalmic antiviral composition in preparation of ophthalmic antiviral medicaments.
As a selectable preferred scheme, the invention provides a preparation method of the ophthalmic antiviral medicament, which comprises the steps of dissolving an emblic leafflower fruit extract, adjusting the pH value to 6.0-8.0 by using a pH regulator, filtering, dissolving borneol by using a small amount of ethanol, adding the dissolved borneol into the filtrate, adding an osmotic pressure regulator, an antioxidant, a solubilizer, a tackifier and a bacteriostatic agent into the filtrate, fully stirring the mixture, adjusting the pH value to 6.0-8.0 by using the pH regulator, adding water for injection into the mixture to adjust the volume to 1L, filtering, subpackaging the filtrate and sterilizing the filtrate to obtain the ophthalmic antiviral medicament.
Wherein the pH regulator includes but is not limited to one or more of phosphate buffer, Murphy's buffer and Papanicolaou buffer, and more preferably, the pH value is regulated to 6.0-7.4 by the pH regulator.
The invention has the following beneficial effects:
the experimental result shows that the prepared antiviral composition for eyes has obvious inhibition effect on various viruses entering eyes by taking the emblic leafflower fruit extract as an active substance, particularly on coronavirus and influenza virus; but also has the advantages of naturalness, safety, mild drug effect and the like. In addition, after metal salts such as zinc sulfate, calcium gluconate, zinc gluconate and the like are added, the synergistic effect with the emblic leafflower fruit extract is realized, the virus is further inhibited, and the antiviral effect is improved.
Based on the above, the invention also provides an ophthalmic antiviral medicament, which has the advantages of simple preparation method, low cost, broad-spectrum antiviral activity, obvious treatment effect on new coronavirus, influenza virus and the like, and good prevention and control significance on the spread and harm of diseases caused by virus infection on human bodies, and can effectively inhibit the viruses from invading through eyes.
Detailed Description
The present invention is further illustrated by the following specific examples, which are not intended to limit the invention in any way. Reagents, methods and apparatus used in the present invention are conventional in the art unless otherwise indicated.
Unless otherwise indicated, reagents and materials used in the following examples are commercially available.
The anti-live virus experiment of the invention is carried out by committing the Guangdong province disease control center.
Example 1 preparation of an extract of Phyllanthus emblica
Drying fresh fructus Phyllanthi in the sun, grinding, and making into powder. Weighing 100g of emblic leafflower powder, wrapping with filter paper, putting into a Soxhlet extractor, adding 1000g of deionized water, Soxhlet extracting for 4h, recovering the water extract, concentrating on a water bath kettle and fixing the volume to obtain the emblic leafflower fruit water extract.
Example 2 preparation of an extract of Phyllanthus emblica
Drying fresh fructus Phyllanthi in the sun, grinding, and making into powder. Weighing 100g of emblic leafflower powder, wrapping with filter paper, putting into a Soxhlet extractor, adding 200g of neutral deionized water, Soxhlet extracting for 2h, recovering the water extract, concentrating on a water bath kettle and fixing the volume to obtain the emblic leafflower fruit water extract.
EXAMPLE 3 preparation of an extract of Phyllanthus emblica
Drying fresh fructus Phyllanthi in the sun, grinding, and making into powder. Weighing 100g of emblic leafflower powder, wrapping with filter paper, putting into a Soxhlet extractor, adding 1200g of neutral deionized water, Soxhlet extracting for 6h, recovering the water extract, concentrating on a water bath kettle and fixing the volume to obtain the emblic leafflower fruit water extract.
EXAMPLE 4 preparation of an antiviral agent for eyes
The ophthalmic medicament specifically comprises the following raw materials: taking 18g of the emblic leafflower fruit extract prepared in the example 1, 8g of zinc sulfate, 0.3g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator sodium chloride, 2g of antioxidant sodium bisulfite, 3ml of solubilizer Tween, 2g of tackifier sodium hyaluronate, 0.2g of bacteriostatic agent benzalkonium chloride, and adjusting the pH value to 6.0.
The preparation method of the ophthalmic preparation comprises dissolving fructus Phyllanthi extract with water for injection, adjusting pH to 6.0-8.0, filtering, dissolving zinc sulfate, dissolving Borneolum Syntheticum with ethanol, adding into the above filtrate, sequentially adding osmotic pressure regulator, antioxidant, solubilizer, tackifier, and bacteriostatic agent, stirring, adjusting pH to 6.0-8.0, adding water for injection to adjust volume to 1L, filtering, packaging the filtrate, and sterilizing.
EXAMPLE 5 preparation of an ophthalmic antiviral agent
The ophthalmic medicament specifically comprises the following raw materials: taking 10g of the emblic leafflower fruit extract prepared in the embodiment 2, 4g of ferrous sulfate, 0.1g of borneol, 1.0ml of ethanol, 3g of osmotic pressure regulator sodium chloride, 0.5g of antioxidant sodium sulfite, 6ml of solubilizer Tween, 1g of tackifier hydroxypropyl methylcellulose and 0.3g of bacteriostatic agent benzalkonium chloride, and adjusting the pH value to 7.4.
The preparation method of the ophthalmic medicament comprises the following steps: the same as in example 4.
EXAMPLE 6 preparation of an ophthalmic antiviral agent
The ophthalmic medicament specifically comprises the following raw materials in parts by weight: 20g of the emblic leafflower fruit extract prepared in the embodiment 1, 15g of calcium gluconate, 0.5g of borneol, 1.0ml of ethanol, 5g of osmotic pressure regulator sodium chloride, 3g of antioxidant sodium bisulfite, 2ml of solubilizer Tween, 5g of tackifier sodium hyaluronate and 0.1g of bacteriostatic agent benzalkonium chloride are taken, and the pH value is adjusted to 5.0.
The preparation method of the ophthalmic medicament comprises the following steps: the same as in example 4.
EXAMPLE 7 preparation of an antiviral agent for eyes
The ophthalmic medicament specifically comprises the following raw materials in parts by weight: taking 8g of the emblic leafflower fruit extract prepared in the example 1, 2g of magnesium oxide, 0.3g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator boric acid, 5g of antioxidant sodium bisulfite, 10ml of solubilizer Tween, 0.1g of tackifier sodium hyaluronate, 0.5g of bacteriostatic agent benzalkonium chloride, and adjusting the pH value to 8.0.
The preparation method of the ophthalmic medicament comprises the following steps: the same as in example 4.
EXAMPLE 8 preparation of an ophthalmic antiviral agent
The ophthalmic medicament specifically comprises the following raw materials in parts by weight: taking 8g of the emblic leafflower fruit extract prepared in the example 1, 2g of sodium tungstate, 0.2g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator boric acid, 5g of antioxidant sodium bisulfite, 10ml of solubilizer Tween, 0.1g of tackifier sodium hyaluronate, 0.5g of bacteriostatic agent benzalkonium chloride, and adjusting the pH value to 7.0.
The preparation method of the ophthalmic medicament comprises the following steps: the same as in example 4.
EXAMPLE 9 preparation of an ophthalmic antiviral agent
The ophthalmic medicament specifically comprises the following raw materials in parts by weight: taking 8g of the emblic leafflower fruit extract prepared in the example 1, 2g of rubidium iodide, 0.3g of borneol, 1.0ml of ethanol, 4g of osmotic pressure regulator boric acid, 5g of antioxidant sodium bisulfite, 10ml of solubilizer Tween, 0.1g of tackifier sodium hyaluronate, 0.5g of bacteriostatic agent benzalkonium chloride, and adjusting the pH value to 6.0.
The preparation method of the ophthalmic medicament comprises the following steps: the same as in example 4.
Comparative example 1 preparation of ophthalmic preparation
The main components and the preparation method of the ophthalmic medicament are the same as example 4, and compared with example 4, the difference is that:
(1) comparative group 1: it does not contain fructus Phyllanthi extract.
(2) Comparative group 2: contains no zinc sulfate.
EXAMPLE 10 ophthalmic antiviral agent Performance testing
1. Stability test
The preparation of example 4 was used as an example.
An appropriate amount of the antiviral agent for eye prepared in example 4 was sampled and tested at high temperature (65 ℃), low temperature (3 ℃) and strong light (4500L ×) for 15 days, and the stability of the samples was examined and shown in table 1.
TABLE 1 ophthalmic antiviral composition stability test
As can be seen from the results in Table 1, after the antiviral ophthalmic composition prepared by the invention is placed under the conditions of high temperature, low temperature and illumination for 15 days, all indexes still meet the standards, so that the composition obtained by the invention has stable quality and meets the requirements.
2. Rabbit eye irritation test
The antiviral agent for eyes prepared in example 4 was used as an experimental sample, and the control drug was physiological saline.
Experimental animals: new Zealand rabbits 1.0-1.5Kg (purchased from laboratory animal monitoring institute in Guangdong province), male and female half, before experiment, animals were raised for 7 days, and animal behavior, activity, diet, mental state and eye health were observed and recorded.
The experimental method comprises the following steps:
dividing rabbits into 2 groups at random, each group comprises 5 rabbits, and dividing the groups into a control group and an experimental group; the control group was dropped with 1.0ml of physiological saline, and the experimental group was dropped with 1.0ml of the ophthalmic antiviral composition prepared in example 4.
The rabbit eye conjunctiva changes were observed 3 times a day (8:00, 13:00, 17:00) for 20 consecutive days, 4 hours after the last administration, 1% fluorescein sodium solution was added 10 hours later, and the results were examined 11 hours later with a slit lamp biomicroscope and recorded. After stopping the drug, the animals were observed for irritation, conjunctival congestion, secretion and corneal staining at 1, 8, 15 and 20 days, and scored as shown in Table 2.
TABLE 2 evaluation criteria for ocular irritation
| Degree of irritation | Scoring |
| Has no irritation | 0-3 |
| Mild irritation | 4-8 |
| Moderate irritation | 9-12 |
| Stimulation of intensity | 13-16 |
After the composition is dripped into each experimental group in the eyes of the rabbits, the stimulation response of animals is observed on 1, 8, 15 and 20 days respectively, the total integral of the stimulation response of the conjunctiva, the cornea, the iris, the conjunctiva and the like of a tested animal is obtained by adding the stimulation response scores of the cornea, the iris and the conjunctiva of each rabbit, and the total integral of one group is divided by the number of animals to obtain the stimulation score of the antiviral combination for the rabbits, wherein the higher the score is, the stronger the stimulation is. The results are shown in Table 3, and it is clear from Table 3 that the cornea, iris and conjunctiva of the eye are normal, and thus the drug of the present invention is not irritating to the eye.
TABLE 3 Rabbit eye irritation evaluation score
| Eye irritation response Condition | Score value |
| Cornea | 0 |
| Iris (iris) | 1 |
| Conjunctiva (conjunctiva) | 0 |
EXAMPLE 11 cytotoxicity testing of ophthalmic Agents
1. Experimental methods
1) The MTT method is used for testing the toxicity of the ophthalmic antiviral composition on cells, and the specific experimental steps are as follows:
(1) according to 1 × 105Concentration per well HEK293 cells were plated in 96-well plates in 100. mu. L DMEM medium at 37 ℃ with 5% CO2Culturing until a monolayer of cells is formed;
(2) discarding the culture solution, washing with PBS for 2 times, selecting the antiviral composition prepared in examples 4-6 as the antiviral composition to be tested, diluting with DMEM in gradient, inoculating on cells at a concentration of 100 μ L/well and with multiple wells each having a concentration of 4 or more, setting the same concentration control group, and washing with 5% CO at 37 deg.C2Culturing for 48 h;
(3) mu.g of L MTT solution (2.5mg/m L) was added to each well at 37 ℃ with 5% CO2Incubating for 4h, discarding the supernatant, adding 120 mu L DMSO/well, and oscillating for 20 min;
(4) measured on a multifunctional reading instrumentAbsorbance (OD) at 490nm of each well, and calculating 50% toxic concentration as half toxic concentration of drug (TC) by Reed-Muench method50)。
2. Results of the experiment
TC50 values for HEK293 cells for ophthalmic antiviral compositions
TC measurement of HEK293 cells by three ophthalmic antiviral compositions of examples 4-6 by MTT assay50The values are 137.43 mu g/m L, 139.52 mu g/m L and 143.39 mu g/m L respectively, which shows that the ophthalmic antiviral composition prepared by the invention has very low cytotoxicity and very small cytotoxic effect.
EXAMPLE 12 in vitro antiviral assay of ophthalmic Agents
1. Experimental methods
In this example, the in vitro antiviral experiments were performed on the ophthalmic preparations prepared in examples 4 to 6 and comparative examples 1 to 4, and the specific experimental procedures were as follows:
(1) HEK293 cells according to 4.5 × 104The individual cells/well concentration were added to a 96 well plate in DMEM with 1% fetal bovine serum at 37 ℃ with 5% CO2Culturing for 24 h;
(2) discard the supernatant and add 100TCID to each well separately502019-nCoV and influenza A H1N1 virus liquid with 5% CO at 37 DEG C2Adsorbing for 2 h;
(3) discarding supernatant, washing cells with PBS, adding diluted antiviral composition for eye, adding equal amount of DMEM to blank control group and virus group, and adding 5% CO at 37 deg.C2Incubating for 72h, and collecting virus supernatant;
(4) HEK293 cells according to 2 × 106One cell/well, seeded in 12-well plates, 5% CO at 37 ℃2Culturing for 24 h;
(5) the virus supernatant collected above was diluted in gradient and inoculated into HEK293 cells at 37 ℃ with 5% CO2Adsorbing for 2 h;
(6) the supernatant was discarded and the cells were washed with PBS and 2m L1% (w/v) methylcellulose-DMEM overlay was added, 5% CO at 37 deg.C2Culturing for 72 h;
(7) removing the methylcellulose-DMEM covering, washing the cells 2 times with PBS, and fixing the cells with 10% formaldehyde for 30min at room temperature;
(8) discarding the supernatant, washing the cells with PBS for 2 times, adding 0.5% crystal violet, staining for 5min at room temperature, washing with deionized water for 2 times, drying, counting plaques, and calculating the half Inhibitory Concentration (IC) of 50% virus-inhibited drug by Reed-Muench method50)。
2. Results of the experiment
In vitro inhibitory effect of ophthalmic antiviral agent on 2019-nCoV and H1N1 influenza A virus
Example 4 ophthalmic antiviral agent concentration of 6.25 μ g/m L inhibited replication of 2019-nCoV and influenza a H1N1 in HEK293 cells, reducing the mean viral titer of 2.82lg PFU/m L and 2.60lg PFU/m L, respectively, and when the drug concentration reached 50 μ g/m L, the mean viral titer was reduced by 5.95lg PFU/m L and 5.28lg PFU/m L, respectively, as shown in table 4.
Example 5 ophthalmic antiviral agent concentration of 6.25 μ g/m L inhibited replication of 2019-nCoV and influenza a H1N1 in HEK293 cells, reducing the mean viral titer of 2.65lg PFU/m L and 2.66lg PFU/m L, respectively, and when the drug concentration reached 50 μ g/m L, the mean viral titer was reduced by 6.02lg PFU/m L and 5.71lg PFU/m L, respectively, as shown in table 5.
Example 6 ophthalmic antiviral agent concentration of 6.25 μ g/m L inhibited replication of 2019-nCoV and influenza A H1N1 virus in HEK293 cells, decreased mean viral titers of 2.41lg PFU/m L and 2.43lg PFU/m L, respectively, and decreased mean viral titers of 5.81lg PFU/m L and 5.4lg PFU/m L, respectively, when the drug concentration reached 50 μ g/m L, see Table 6.
The eye agent of comparative group 1 still failed to inhibit the replication of 2019-nCoV and influenza A H1N1 virus in HEK293 cells at a concentration of 50. mu.g/m L, and the mean virus titer decreased only by 1.36lgPFU/m L and 1.39lgPFU/m L, respectively, as shown in Table 7.
The comparison group 2 eye medicine concentration of 50 μ g/m L can inhibit the replication of 2019-nCoV and influenza A H1N1 virus in HEK293 cells, and the average virus titer of 1.55lg PFU/m L and 1.62lg PFU/m L is respectively reduced, which is shown in Table 8.
Table 4 example 4 inhibitory Effect of ophthalmic Agents on two viruses
Table 5 example 5 inhibition of two viruses by ophthalmic agents
TABLE 6 EXAMPLE 6 inhibitory Effect of ophthalmic Agents on two viruses
TABLE 7 inhibitory Effect of comparative group 1 ophthalmic agent on two viruses
TABLE 8 inhibition of two viruses by comparative group 2 ophthalmic agents
The results in tables 4 to 8 show that the ophthalmic preparation prepared by the formulation of the present application has significantly better antiviral effect than the comparative groups 1 to 2.
EXAMPLE 13 in vitro antiviral assay of ophthalmic Agents
The ophthalmic preparation of example 4 was used as an example to test the antiviral effects of the ophthalmic preparation on Adenovirus (Adenovirus), Varicella Zoster Virus (VZV) and Cytomegalovirus (Cytomegalovirus) in the same manner as in example 12. The results are shown in Table 9.
TABLE 9 inhibitory Effect of comparative group 4 ophthalmic agents on Adenovirus (Adenovir)
As can be seen from the results in table 9, the ophthalmic preparation of the present invention has significant inhibitory effects on Adenovirus (Adenovirus), Varicella Zoster Virus (VZV), and Cytomegalovirus (cytomegavirus).
The above embodiments are preferred embodiments of the present invention, but the present invention is not limited to the above embodiments, and any other changes, modifications, substitutions, combinations, and simplifications which do not depart from the spirit and principle of the present invention should be construed as equivalents thereof, and all such changes, modifications, substitutions, combinations, and simplifications are intended to be included in the scope of the present invention.
Claims (11)
1. An ophthalmic antiviral composition comprising an extract of Phyllanthus emblica and water for injection.
2. The ophthalmic antiviral composition of claim 1, further comprising a metal salt.
3. The ophthalmic antiviral composition according to claim 2, wherein said metal salt is one or more of zinc salt, iron salt, calcium salt, magnesium salt, tungsten salt, rubidium salt.
4. The ophthalmic antiviral composition according to claim 1, wherein the emblic extract is an aqueous emblic extract.
5. The ophthalmic antiviral composition according to claim 5, wherein the aqueous extract of Phyllanthus emblica is prepared by the following method: extracting fructus Phyllanthi powder with deionized water 2-12 times of the weight of fructus Phyllanthi powder for 2-6 hr, recovering water extract, and concentrating.
6. The ophthalmic antiviral composition according to any one of claims 1 to 6, further comprising an osmotic pressure regulator, an antioxidant, a solubilizer, a bacteriostatic agent, and a viscosity-increasing agent.
7. The ophthalmic antiviral composition according to claim 7, wherein the composition comprises, in parts by weight, 8-20 parts of emblic leafflower fruit extract, 3-5 parts of osmotic pressure regulator, 0.1-5 parts of antioxidant, 0.5-10 parts of solubilizer, 0.1-0.5 part of bacteriostatic agent, 0.1-5 parts of tackifier, 0.1-0.5 part of borneol, and the balance of water for injection per 1L parts of composition.
8. The ophthalmic antiviral composition according to claim 7, further comprising 2 to 20 parts of a metal salt.
9. The ophthalmic antiviral composition according to claim 7 or 8, wherein the tonicity adjusting agent is sodium chloride or boric acid; the antioxidant is one or more of sodium bisulfite, sodium sulfite, sodium thiosulfate, sodium metabisulfite and vitamin C; the solubilizer is tween-80 or tween-20; the bacteriostatic agent is benzalkonium chloride or benzalkonium bromide; the tackifier is one or more of sodium hyaluronate, hydroxypropyl methylcellulose, polyvidone and polyvinyl alcohol.
10. Use of the ophthalmic antiviral composition of any one of claims 1 to 9 for the preparation of an ophthalmic antiviral agent.
11. The ophthalmic antiviral agent according to claim 10, wherein the preparation method comprises dissolving the extract of Phyllanthus emblica, adjusting pH to 6.0-8.0 with a pH adjuster, filtering, dissolving borneol with ethanol, adding into the above filtrate, adding an osmotic pressure adjuster, an antioxidant, a solubilizer, a tackifier, and a bacteriostatic agent, stirring thoroughly, adjusting pH to 6.0-8.0 with a pH adjuster, adding water for injection to adjust the volume to 1L, filtering, packaging the filtrate, and sterilizing.
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| PCT/CN2021/099481 WO2021249501A1 (en) | 2020-06-11 | 2021-06-10 | Antiviral preparation |
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| WO2022079664A1 (en) * | 2020-10-15 | 2022-04-21 | Bausch & Lomb Ireland Limited | Benzalkonium chloride for use in treating conjunctivitis and/or covid-19 |
| EP4205753A1 (en) * | 2021-12-30 | 2023-07-05 | Léon Cariel | Antiviral plant extract composition and method for preparing such composition |
| EP4205754A1 (en) * | 2021-12-30 | 2023-07-05 | Léon Cariel | Antiviral plant extract composition and method for preparing such composition |
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