CN114748611A - Composition with antioxidant, moisturizing and lubricating effects and application thereof - Google Patents

Composition with antioxidant, moisturizing and lubricating effects and application thereof Download PDF

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Publication number
CN114748611A
CN114748611A CN202210244470.7A CN202210244470A CN114748611A CN 114748611 A CN114748611 A CN 114748611A CN 202210244470 A CN202210244470 A CN 202210244470A CN 114748611 A CN114748611 A CN 114748611A
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China
Prior art keywords
solution
collagen
ergothioneine
composition
ectoin
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丁利平
张山
董亮
秦丽娜
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Shenzhen Upfo Biotech Co ltd
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Shenzhen Upfo Biotech Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/41641,3-Diazoles
    • A61K31/4172Imidazole-alkanecarboxylic acids, e.g. histidine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/726Glycosaminoglycans, i.e. mucopolysaccharides
    • A61K31/728Hyaluronic acid
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00Medicinal preparations containing peptides
    • A61K38/16Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/39Connective tissue peptides, e.g. collagen, elastin, laminin, fibronectin, vitronectin, cold insoluble globulin [CIG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0048Eye, e.g. artificial tears
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00Drugs for disorders of the senses
    • A61P27/02Ophthalmic agents
    • A61P27/04Artificial tears; Irrigation solutions
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00General protective or antinoxious agents
    • A61P39/06Free radical scavengers or antioxidants

Abstract

The invention discloses a composition with antioxidant, moisturizing and lubricating effects and application thereof, and belongs to the field of medical instruments. The invention provides an antioxidant moisturizing lubricating composition containing ectoin, collagen and ergothioneine, which comprises the following components in percentage by mass: 0.01-1% of collagen, 0.1-5% of ectoin, 0.005-0.1% of ergothioneine, 0.01-1% of humectant, 0.01-10% of buffering agent, 0.01-2% of osmotic pressure regulator, 0.001-5% of surfactant and 0.05-5% of chelating agent. The moisturizing eye composition provided by the invention can be used as eye drops for relieving dryness and discomfort of eyes besides being used as a lubricating liquid when a contact lens is worn, and secondly, the composition does not contain a preservative and bactericide because the ectoine and the ergothioneine in the composition also have a bactericidal effect.

Description

Composition with antioxidant, moisturizing and lubricating effects and application thereof
Technical Field
The invention belongs to the field of medical instruments, and particularly relates to a composition with antioxidant, moisturizing and lubricating effects and application thereof.
Background
With the popularization and application of display terminals, computers become indispensable office equipment for daily office work, mobile phones also become objects to be carried with people in life, and in recent years, people have longer and longer use time of computers and mobile phones, so that the antioxidant defense system of eyes is weakened, and the vision is degraded, the objects are blurred, and then other eye diseases are caused. According to the previous research reports of the world health organization, the number of Chinese myopia patients reaches as many as 6 hundred million, the myopia rate of teenagers is the first in the world, and the number of patients with astigmatism, hyperopia and ametropia is increased year by year, so that Chinese becomes the first disease of the world. The contact lenses for correcting eyesight and protecting eyes are popular with patients with abnormal eyesight due to the beauty, convenience, wide and vivid objects. Insufficient moisture retention can result in insufficient fluid filling between the cornea and the contact lens, and insufficient lubricity can increase the friction of the lens with the ocular surface. Therefore, the user wearing the lens is prone to problems such as dry eyes, discomfort, corneal injury, inflammation, etc.
Lubricating fluids and artificial tears are widely used because they can moisten eyes, relieve symptoms such as eyestrain and discomfort. Currently, the commonly used moisturizing and lubricating factors mainly include Hyaluronic Acid (HA), sodium Pyrrolidone Carboxylate (PCA), polyvinyl alcohol (PVA), glycerin, propylene glycol, sorbitol, and the like. PVA is a soluble resin and has an irritating effect on the eyes. PCA is a natural humectant with excellent moisture absorption performance, and the moisture retention performance is stronger than that of the traditional humectants such as glycerin, propylene glycol and sorbitol. HA is a macromolecular polysaccharide, is the main component of various connective tissues in human bodies, HAs a good water retention effect, and is called as an ideal natural moisturizing factor. However, the existing ophthalmic lubricating oil containing hyaluronic acid is still insufficient in moisturizing performance, and the treatment result is not satisfactory especially for dry eye patients.
Disclosure of Invention
[ problem ] to
The invention aims to solve the technical problems that the existing lubricating liquid and artificial tears have insufficient eye irritation and lubricating and moisturizing effects and cannot effectively remove free radicals in eyes.
[ solution ]
In order to solve the technical problems, the invention provides a composition with antioxidant, moisturizing and lubricating effects and application thereof.
The composition with the functions of oxidation resistance, moisture retention and lubrication comprises, by mass, 0.1% -5% of ectoin, 0.01% -0.5% of collagen, 0.005% -0.1% of ergothioneine, 0.01% -1% of a humectant, 0.05% -5% of a chelating agent, 0.01% -10% of a buffering agent, 0.001% -5% of a surfactant, 0.01% -2% of an osmotic pressure regulator and the balance of water for injection.
Further, the composition comprises the following components in percentage by mass: 0.5-2% of ectoin, 0.05-0.5% of collagen, 0.01-0.1% of ergothioneine, 0.05-0.5% of humectant, 0.1-5% of buffering agent, 0.05-2% of chelating agent, 0.01-5% of surfactant, 0.1-2% of osmotic pressure regulator and the balance of water for injection.
Further, the mass content of the ectoin is 0.5% -1%.
Furthermore, the collagen is human type III collagen, and the molecular weight of the collagen is 20-50 KD, preferably 40 KD.
Further, the pH of the composition is in the range of 6 to 8, preferably 6.5 to 7.5, more preferably 7.0.
Further, the osmotic pressure of the composition is 230-350 mOsm/(Kg. H)2O), preferably 300 mOsm/(Kg. H)2O)。
Further, the osmotic pressure regulator of the composition is selected from one or more of sodium chloride, potassium chloride, boric acid and borax, and sodium chloride is preferred.
Further, the buffer is selected from one or more of phosphate, borate, citrate, preferably borate buffer.
Furthermore, the humectant is a hyaluronic acid substance, is selected from one or more of hyaluronic acid, hyaluronate and hyaluronate derivatives, and is preferably sodium hyaluronate.
Further, the chelating agent is one or more of ethylenediamine tetraacetic acid and sodium salt thereof, glycine, citric acid and succinic acid, and preferably disodium ethylenediamine tetraacetic acid.
Further, the surfactant is selected from one or more of poloxamer, polyethylene glycol, polysorbate and alkyl glycoside, preferably poloxamer.
The invention also provides a preparation method of the composition, which comprises the following steps:
(1) weighing 0.1-5% of ectoin, 0.01-0.5% of collagen, 0.005-0.1% of ergothioneine and humectant
0.01-1%, 0.05-5% of chelating agent, 0.01-10% of buffering agent, 0.001-5% of surfactant, 0.01-2% of osmotic pressure regulator and water for injection;
(2) dissolving the buffer weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the humectant, the chelating agent, the surfactant and the 80% solution A weighed in the step (1) at 60 ℃ until the humectant, the chelating agent, the surfactant and the 80% solution A are completely dissolved to prepare a solution B, and cooling to room temperature;
(4) Dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the osmotic pressure regulator weighed in the step (1) to regulate the osmotic pressure to 230-350 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
[ advantageous effects ]
1. The ectoin has strong ability of complexing water molecules and has the water retention and water locking performance, and the symptoms such as eye dryness and the like can be effectively relieved by selecting the ectoin as a moisturizing component in the formula.
2. The collagen can make eye cornea more transparent, and has synergistic moisturizing and lubricating effects when used together with ectoin. The combination of ectoin and collagen produces the lubricated effect of cooperating moisturizing, and ectoin's use can keep the eye moist to alleviate the eye dryness symptom of wearing contact lens production, promotes and wears the comfort level, and collagen's use can reduce the wearing and tearing between contact lens and the cornea for the cornea keeps transparent, and eyes become brighter, and the two uses in coordination can restore and keep the eye moist, improve tear exchange and play the protection eyes effect.
3. Ergothioneine has strong effects of resisting oxidation, scavenging free radicals and caring optic nerve, can relieve free radicals generated by corneal anoxia caused by long-term wearing of the eye mask or visual fatigue caused by long-term viewing, and can repair red swelling inflammation of eyes.
4. The moisturizing composition of the invention, namely the ectoin, the collagen and the antioxidant ergothioneine, has no stimulation to eyes and no cytotoxicity.
5. The ectoin and the ergothioneine have the synergistic antibacterial and anti-inflammatory effects, and can play a more effective role in repairing and protecting eyes when being used together with collagen.
6. The composition provided by the invention has excellent effects on relieving eye fatigue discomfort, moisturizing and lubricating, repairing and anti-inflammatory, and various components in the composition not only can play a role in synergistic moisturizing and lubricating, but also can play a role in synergistic anti-inflammatory and repairing. And the preparation method of the eye composition is simple and easy to implement.
Detailed Description
The following detailed description is given by way of example in order to more clearly illustrate the general concept of the present application. Various details of embodiments of the present application are set forth for purposes of illustration and not limitation, in order to provide a more thorough understanding of the present invention. Accordingly, those of ordinary skill in the art will recognize that various changes and modifications of the embodiments described herein can be made without departing from the scope and spirit of the present application. Also, descriptions of well-known functions and constructions are omitted in the following description for clarity and conciseness.
Ectoin is derived from the English name Ectoine, and the Chinese name is tetrahydro-methyl pyrimidine carboxylic acid (2-methyl-1, 4,5, 6-tetrahydro-pyrimidine-4-carboxylic acid), is an amino acid derivative, can regulate the osmotic pressure of cells, and is an important substance for extreme environment microorganisms to adapt to the survival of extreme environments such as high temperature, high salt, strong ultraviolet rays and the like. The ectoin has unique high-polarity molecular structure and powerful water retaining and locking performance. The ectoin has stronger ability of complexing water molecules, one molecule of ectoin can complex four or five water molecules, and a layer of 'hydrated shell' is formed around cells and proteins and is similar to a stable protective film, so that the water loss is reduced.
Collagen is a protein with the most abundant content in human body, has the functions of moisturizing and nourishing, is rich in collagen active peptide in the cornea, and can keep the cornea transparent, so that the eyes are brighter and more attractive. The collagen is formed by winding three amino acid chains, and the 'triple helix structure' can powerfully lock water molecules. The collagen not only can lock water, but also can be used for enhancing the moisturizing and water locking performances of the collagen under the synergistic effect with hyaluronic acid. The gene sequence of the recombined III type human collagen is highly consistent with the gene sequence of the human III type collagen, is elastic collagen, has good compatibility with organism tissues, is considered as a self substance by a human immunity defense line, can be directly absorbed, assimilated and utilized by a human body, has high utilization rate of the III type collagen, and has high tissue injury repair speed.
Ergothioneine is a rare natural chiral amino acid in a human body, has various effects of scavenging free radicals, resisting oxidation, resisting inflammation, whitening, resisting radiation and the like, is an amino acid necessary for cell growth and cellular immunity, and has a protective effect on optic nerve cells, and has higher content in eye tissues such as retina, cornea, crystalline lens and the like, so that the eye is protected from oxidative damage, and eye diseases can be caused by lower ergothioneine level. Thus, ergothioneine has an eye-protecting effect.
The collagen in the following examples is of human type III collagen, and was purchased from Zhongkongxin.
Example 1:
(1) weighing 1% of ectoin, 0.1% of collagen, 0.02% of ergothioneine, 0.1% of humectant sodium hyaluronate, 0.32% of surfactant poloxamer-4070.1%, 0.05% of chelating agent EDTA-2Na, 0.01-10% of borate buffering agent, 0.01-2% of osmotic pressure regulator NaCl0.01 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the sodium hyaluronate, poloxamer-407, EDTA-2Na and 80% solution A weighed in the step (1) at 60 ℃ until the sodium hyaluronate, poloxamer-407, EDTA-2Na and 80% solution A are completely dissolved, preparing solution B, and cooling to room temperature;
(4) Dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Example 2:
(1) weighing 2% of ectoin, 0.01% of collagen, 0.05% of ergothioneine, 0.1% of sodium hyaluronate, 0.78% of poloxamer-4070.1%, 0.05% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80% solution A at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare solution B, and cooling to room temperature;
(4) and (2) dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C.
(5) Uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering, sterilizing and packaging to obtain the finished product.
Example 3:
(1) Weighing 0.5% of ectoin, 0.3% of collagen, 0.2% of ergothioneine, 0.1% of sodium hyaluronate, 0. 4070.1% of poloxamer, 0.05% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0 and water for injection. (ii) a
(2) Dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80% solution A at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare solution B, and cooling to room temperature;
(4) and (2) dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C.
(5) Uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering, sterilizing and packaging to obtain the finished product.
Example 4:
(1) weighing 3% of ectoin, 0.02% of collagen, 0.1% of ergothioneine, 0.1% of sodium hyaluronate, 0.78% of poloxamer-4070.1%, 0.05% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0.01 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) Continuously stirring the sodium hyaluronate, poloxamer-407, EDTA-2Na and 80% solution A weighed in the step (1) at 60 ℃ until the sodium hyaluronate, poloxamer-407, EDTA-2Na and 80% solution A are completely dissolved, preparing solution B, and cooling to room temperature;
(4) dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Comparative example 1: does not contain ectoin
(1) Weighing 0.1% of collagen, 0.02% of ergothioneine, 0.1% of sodium hyaluronate, 0.05% of poloxamer-4070.1%, 0.01-10% of EDTA-2 Na0.05%, 0.01-10% of borate buffer, 0.01-2% of NaCl0.01 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80% solution A at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare solution B, and cooling to room temperature;
(4) dissolving the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the collagen and the ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H) 2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Comparative example 2: contains no collagen
(1) Weighing 1% of ectoin, 0.02% of ergothioneine, 0.1% of sodium hyaluronate, 0.05% of poloxamer-4070.1%, 0.01-10% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0.01 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) mixing the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80%; continuously stirring the solution A at 60 ℃ until the solution A is completely dissolved to prepare a solution B, and cooling to room temperature;
(4) dissolving the ectoin and ergothioneine weighed in the step (1) in the residual solution A until the ectoin and ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering, sterilizing and packaging to obtain the finished product.
Comparative example 3: does not contain ergothioneine
(1) Weighing 1% of ectoin, 0.1% of collagen, 0.1% of sodium hyaluronate, 0.05% of poloxamer-4070.1%, 0.01-10% of EDTA-2Na, 0.01-10% of borate buffering agent, 0.01-2% of NaCl0.01 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) Continuously stirring the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80% solution A at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare solution B, and cooling to room temperature;
(4) dissolving the ectoin and the collagen weighed in the step (1) in the residual solution A until the ectoin and the collagen are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the NaCl weighed in the step (1) to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Comparative example 4: it does not contain ectoin, collagen and ergothioneine
(1) Weighing 0.1% of sodium hyaluronate, 0.05% of poloxamer-4070.1%, 0.05% of EDTA-2Na, 0.01-10% of borate buffering agent, 0.01-2% of NaCl0.01-2% and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and 80% solution A at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare solution B, and cooling to room temperature;
(4) adding the NaCl weighed in the step (1) into the solution B to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering, sterilizing and packaging to obtain the finished product.
Comparative example 5: it does not contain ectoin, collagen and ergothioneine, and uses polyvinyl alcohol as lubricant factor
(1) Weighing 1% of polyvinyl alcohol, 0.1% of sodium hyaluronate, 0.78% of poloxamer-4070.1%, 0.05% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0 and water for injection;
(2) dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the polyvinyl alcohol, the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A weighed in the step (1) at 60 ℃ until the polyvinyl alcohol, the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the 80% solution A are completely dissolved to prepare a solution B, and cooling to room temperature;
(4) adding the NaCl weighed in the step (1) into the solution B to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Comparative example 6: without ectoin, the remaining ingredients were mixed directly
0.1 percent of collagen, 0.02 percent of ergothioneine, 0.1 percent of sodium hyaluronate, 0. 4070.1 percent of poloxamer, 0.05 percent of EDTA-2Na, 0.01 to 10 percent of borate buffer, 0.01 to 2 percent of NaCl0.01 and water for injection are mixed uniformly, the pH of the obtained solution is 6.5 to 7.5, and the osmotic pressure is 300 mOsm/(Kg. H)2O). Filtering, sterilizing, and packaging.
Comparative example 7: adjusting the order of addition of ectoin, collagen and ergothioneine
(1) Weighing 1% of ectoin, 0.1% of collagen, 0.02% of ergothioneine, 0.1% of sodium hyaluronate, 0.78% of poloxamer-4070.1%, 0.05% of EDTA-2Na, 0.01-10% of borate buffer, 0.01-2% of NaCl0.01 and water for injection;
(2) Dissolving the borate buffering agent weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in a 20% solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution B;
(4) adding the sodium hyaluronate weighed in the step (1), poloxamer-407, EDTA-2Na and the rest solution A into the solution B, continuously stirring at 60 ℃ until the sodium hyaluronate, the poloxamer-407, the EDTA-2Na and the rest solution A are completely dissolved, and cooling to room temperature to obtain a solution C;
(5) adding the NaCl weighed in the step (1) into the solution C to adjust the osmotic pressure to 300 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
Among them, the compositions obtained in examples 1 to 4 and comparative examples 1 to 7 are applicable to contact lens lubricating fluids or artificial tears. In a preferred embodiment, the present invention provides a method of using the composition as a contact lens lubricating fluid as follows:
cleaning hand, turning up lower eyelid, dripping into the lubricating liquid or artificial tear of the composition for 3-5 min, and blinking eye to disperse the lubricating liquid or artificial tear uniformly.
Evaluation of lubricity and moisture Retention
Test 1: determination of the coefficient of friction
The friction coefficient measurement refers to the four-ball method of national standard GB3142-90, the lubrication performance of examples 1-4 and comparative examples 1-2 is evaluated by a four-ball friction abrasion tester, the measurement indexes are friction coefficient (mu) and grinding spot diameter (phi), the load of a used friction system is 30N, and the diameter of a used ceramic ball is 12.7 mm. The experimental conditions were set as follows: the rotation speed is 1500r/min, the temperature is 37 ℃, and the test time is 30 min. The results are shown in table 1 below.
Table 1 shows the coefficients of friction of examples and comparative examples
Figure BDA0003544497060000071
Figure BDA0003544497060000081
As shown in Table 1, the friction coefficients and the scrub spot diameters of examples 1-4 and comparative examples 6-7 were significantly smaller than those of comparative examples 1-5, indicating that the lubricating properties of the compositions containing ectoin, collagen and ergothioneine were significantly better than those of sodium hyaluronate. The friction coefficients and the wear scar diameters of examples 1-4 are smaller than those of comparative examples 1-4, indicating that ectoin, collagen and ergothioneine act synergistically with sodium hyaluronate as a composition to reduce the friction coefficient and act in combination with an unexpected technical effect on lubrication.
The above results show that ectoin, collagen and ergothioneine contained in examples 1 to 4 of the present invention have excellent lubricating properties and have potential to relieve dry eyes as eye drops or artificial tears.
Test 2: eye irritation test
New Zealand rabbits are used as test subjects and are randomly divided into 11 groups of 8 rabbits, and the age and the weight of the rabbits in each group have no obvious difference. The test was carried out using the ophthalmic care compositions prepared in examples 1 to 4 and comparative examples 1 to 7, respectively, and 0.05ml of the ophthalmic care product was dropped to the left eye and the same amount of water for injection was dropped to the right eye of each rabbit in the group as a blank control. After each group is dropped into the test substance, the eyes are closed for 5-10s, 2 times a day, and the treatment lasts for 28 days. The local eye response after each dose was observed and recorded. The eye irritation response scoring standard is carried out according to the eye irritation response judgment standard in the 'New medicine (western medicine) preclinical research guide principle', wherein 0-3 is non-irritant, 4-8 is mild irritation, 9-12 is moderate irritation, and 13-16 is intensity irritation.
The results of observation and recording 1h, 1 day, 7 days, 14 days, and 28 days after the first eye drop in each treatment group are shown in table 2.
TABLE 2 results of irritation test
Figure BDA0003544497060000082
Figure BDA0003544497060000091
The results of the eye irritation test show that the formulation of the compositions of examples 1-4 are non-irritating to the eyes of New Zealand rabbits.
Test 3 anti-fatigue test
New Zealand rabbits are used as test subjects and are randomly divided into 11 groups of 8 rabbits, and the age and the weight of the rabbits in each group have no obvious difference. After irradiation with light having an intensity of 3000-50001iuX for 5 days, the compositions of examples 1 to 4 and comparative examples 1 to 7 were added dropwise in groups, and the fatigue index of each rabbit eye was scored. The liquid is dripped for 3-7 days by 0.05mL for 5 times a day, and the change of various fatigue indexes of rabbit eyes is observed every day and is scored and recorded.
TABLE 3 anti-fatigue test results
Figure BDA0003544497060000092
Figure BDA0003544497060000101
According to the anti-fatigue test result, the anti-oxidation moisturizing lubricating composition prepared in the example 1 is remarkable in anti-fatigue effect and quick in recovery time.
Test 4: evaluation of Using Effect
The experimental subjects were 77 volunteers who suffered from dry eyes and inflammation due to wearing contact lenses for a long time, and suffered from discomfort symptoms such as eye fatigue and foreign body sensation due to long-term exposure to computers, and were divided into 11 groups. Each group was once dropped daily with 0.1ml of each ophthalmic composition prepared in examples 1 to 4 and comparative example for 3 consecutive days, and the test results were scored according to the evaluation criteria: 1 part-poor, 2 parts-poor, 3 parts-general, 4 parts-good, and 5 parts-good.
The results are shown in Table 4.
Table 4 evaluation results of effects of use
Figure BDA0003544497060000102
Figure BDA0003544497060000111
And (3) displaying the use effect: compared with comparative examples 1 to 7, the ophthalmic composition of examples 1 to 4, especially example 1, can significantly improve the moisturizing effect after entering eyes, relieve uncomfortable symptoms such as dry eyes and inflammation, and is comfortable to use. The antioxidant moisturizing lubricating composition provided by the invention shows superior moisturizing performance to sodium hyaluronate when used as a contact lens lubricating liquid or artificial tear, obviously improves the comfort level of wearing contact lenses, and can obviously relieve uncomfortable symptoms such as eye dryness and fatigue caused by frequent computer facing.
In conclusion, the composition provided by the invention has higher biological safety by taking a certain mass fraction of ectoin, collagen and ergothioneine as an antioxidant moisturizing lubricating composition, and shows excellent lubricating and moisturizing performances and fatigue resistance performances. Meanwhile, the ophthalmic composition can also be used as an artificial tear to relieve uncomfortable symptoms such as dry, tired and inflammation of eyes.
Although the present invention has been described with reference to the preferred embodiments, it should be understood that various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.

Claims (10)

1. The composition with the effects of resisting oxidation, preserving moisture and lubricating is characterized by comprising, by mass, 0.1-5% of ectoin, 0.01-0.5% of collagen, 0.005-0.1% of ergothioneine, 0.01-1% of a humectant, 0.05-5% of a chelating agent, 0.01-10% of a buffering agent, 0.001-5% of a surfactant and 0.01-2% of an osmotic pressure regulator, and the balance of water for injection.
2. The composition according to claim 1, characterized in that it comprises, in mass percent: 0.5-2% of ectoin, 0.05-0.5% of collagen, 0.01-0.1% of ergothioneine, 0.05-0.5% of humectant, 0.1-5% of buffering agent, 0.05-2% of chelating agent, 0.01-5% of surfactant, 0.1-2% of osmotic pressure regulator and the balance of water for injection.
3. The composition as claimed in claim 1, wherein the mass fraction of ectoin is 0.5-1%.
4. The composition according to claim 1, wherein the mass fraction of the collagen is 0.05-0.5%.
5. A composition according to any one of claims 1 to 4, wherein the collagen is of human type III collagen having a molecular weight of 20 to 50kD, preferably 40 kD.
6. The composition according to any one of claims 1 to 5, wherein the composition has a pH in the range of 6 to 8, preferably 6.5 to 7.5, more preferably 7.0.
7. Composition according to any one of claims 1 to 5, wherein the composition has an osmolality of 230-350 mOsm/(Kg-H2O), preferably 300 mOsm/(Kg-H2O).
8. The composition according to claim 1, wherein the osmotic pressure regulator of the composition is selected from one or more of sodium chloride, potassium chloride, boric acid, borax, preferably sodium chloride; the buffer is selected from one or more of phosphate, borate and citrate, preferably borate buffer; the humectant is a hyaluronic acid substance, is selected from one or more of hyaluronic acid, hyaluronate and hyaluronate derivatives, and is preferably sodium hyaluronate. The chelating agent is one or more of ethylenediamine tetraacetic acid and sodium salt thereof, glycine, citric acid and succinic acid, and preferably disodium ethylenediamine tetraacetic acid; the surfactant is selected from one or more of poloxamer, polyethylene glycol, polysorbate, and alkyl glycoside, preferably poloxamer.
9. A process for preparing a composition according to any one of claims 1 to 8,
(1) weighing Izodo, collagen, ergothioneine, a humectant, a chelating agent, a buffering agent, a surfactant, an osmotic pressure regulator and water for injection;
(2) dissolving the buffer weighed in the step (1) in injection water to obtain a solution A, and adjusting the pH value to 6.5-7.5;
(3) continuously stirring the humectant, the chelating agent, the surfactant and the 80% solution A weighed in the step (1) at 60 ℃ until the humectant, the chelating agent, the surfactant and the 80% solution A are completely dissolved to prepare a solution B, and cooling to room temperature;
(4) dissolving the ectoin, the collagen and the ergothioneine weighed in the step (1) in the residual solution A until the ectoin, the collagen and the ergothioneine are completely dissolved to obtain a solution C;
(5) uniformly mixing the solution B and the solution C, adding the osmotic pressure regulator weighed in the step (1) to regulate the osmotic pressure to 230-350 mOsm/(Kg. H)2O), filtering and sterilizing, and subpackaging to obtain the finished product.
10. Use of a composition according to any one of claims 1 to 8 in the manufacture of an eye care product.
CN202210244470.7A 2022-03-14 2022-03-14 Composition with antioxidant, moisturizing and lubricating effects and application thereof Pending CN114748611A (en)

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