CN104645313A - Mussel mucoprotein gel for repairing and reliving itching and preparation method of mussel mucoprotein gel - Google Patents
Mussel mucoprotein gel for repairing and reliving itching and preparation method of mussel mucoprotein gel Download PDFInfo
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- CN104645313A CN104645313A CN201510044047.2A CN201510044047A CN104645313A CN 104645313 A CN104645313 A CN 104645313A CN 201510044047 A CN201510044047 A CN 201510044047A CN 104645313 A CN104645313 A CN 104645313A
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Abstract
The invention discloses a mussel mucoprotein gel for repairing and reliving itching. The mussel mucoprotein gel is prepared from the following components in percentage by weight: 0.15%-0.2% of mussel mucoprotein, 0.5%-2% of a macromolecule host material, 3%-10% of a humectant, 1%-5% of a surfactant, 0.1%-0.5% of a preservative, 1%-2% of a protein protectant, 0.5%-3% of a stabilizer, 0.5%-1% of a bacteriostatic agent, 0.8%-5.2% of a pH modifier and the balance of purified water. The mussel mucoprotein gel has good biological adhesion, is rapidly and effectively adhered to a wound surface, is capable of rapidly reliving itching and easing pain, and has the advantages of being low in immunogenicity, good in biocompatibility with a human body, convenient to use, free of thrill to skin, safe, nontoxic and free of bad reaction.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, be specifically related to antipruritic sea-mussel mucin gel of a kind of reparation and preparation method thereof.
Background technology
Sea-mussel mucin (Mussel adhesive protein MAP), also cry Mytilus edulis byssus protein (Mytilus edulis footprotein Mefp) from seashells Mytilus edulis, Mytilus edulis, it has the ability at coastal waters tolerance wave effect, it generates and stores a kind of albumin glue in special body of gland, be discharged into by byssus byssus on the surface of solids of rock one class, form the combination of water resistant, thus oneself is fixed.Research display on glass, the speckle that albumin glue is formed, extends from speckle and opens, have very strong tensile strength (106-107mewton/meter2), and in speckle, material contains sea-mussel mucin MAP.
Lys content 20%, DOPA content 11% in sea-mussel mucin (MAP).Sea-mussel mucin is by forming the microbiological support Promotive union of water proof adherent zone positive charge.The isoelectric point, IP that mussel is glued is 9.5, at physiological PH value, existence because of lysine has the positive charge of very high carrying capacity, microcosmic support is formed at wound surface, the cell of suction band negative charge, quick wall attaching, creeping substitution and the growths such as such as epidermis cell, fibroblast, vascular endothelial cell, neurocyte, wound healing.Be cross-linked to form the discontinuous gauze bio support of microcosmic in the environment that the DOPA of simultaneous oxidation and unoxidized DOPA exists at oxygen, strengthen water proof and stick.Active group important in molecule containing sine group and L-DOPA group in sea-mussel mucin, in sea-mussel mucin matter molecule a large amount of sine group make its in human physiological environment with a large amount of positive charge because the reason of potential difference can play itching-relieving action, and L-DOPA is originally as neurotransmitter, may neural activity be participated in, reach antipruritic effect.
The antipruritic material of current sea-mussel mucin wound repair is spray dosage form, but spray can not meet the requirement of each clinical department in clinical practice, as gynecological etc., therefore needs to develop more dosage form on maintenance sea-mussel mucin promoting healing and antipruritic active basis.Gel is now widely used a kind of dosage form, its energy long period and site of action generation close contact, has and better puts into bioadhesive, and can improve the absorption of active component from contact site, avoid liver first-pass effect and intestines and stomach destruction, improve the bioavailability of active component.
At present, antipruritic sea-mussel mucin gel of a kind of reparation good with the human-body biological compatibility and preparation method thereof is lacked.
Summary of the invention
Technical problem to be solved by this invention is to provide antipruritic sea-mussel mucin gel of a kind of reparation good with the human-body biological compatibility and preparation method thereof.
To achieve these goals, the present invention is achieved through the following technical solutions: the invention provides the antipruritic sea-mussel mucin gel of a kind of reparation, described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
Further, the pH value of the antipruritic sea-mussel mucin gel of described reparation is 3.8-5.8.
Further, described high-molecular matrix material is the combination of one or more in Carbomer-940, hydroxypropyl emthylcellulose, methylcellulose, hydroxy methocel.
Further, described wetting agent is the combination of one or more in glycerol, ethylene glycol, sorbitol, glycerol.
Further, described surfactant be that Tween 80, fatty acid Pyrusussuriensis are smooth, the combination of one or more in dodecyl sodium sulfate.
Further, described antiseptic is nipagin A; Described stabilizing agent is the combination of one or more in low molecular dextran, ethylenediaminetetraacetic acid, disodiumedetate, sodium ethylene diamine tetracetate calcium.
Further, described antibacterial is the combination of one or more in nipagin A, dimethyl fumarate, low-grade fatty acid ester; Described PH regulator is the combination of one or more in citric acid, sorbic acid, sodium sesquicarbonate.
The preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprises the steps:
(1) utensil prepares: just all utensils are cleaned, sterilizing;
(2) the swelling and sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 3.8-5.8, at 0.1-0.15MPa pressure, under 120-130 DEG C of condition, 30min autoclaving, for subsequent use after cooling;
(3) albumen aseptic filtration: the protein protective agent of 1%-2% in sea-mussel mucin raw material feed liquid after treatment, then the 1%-2% of original concentration is diluted to by purified water, aseptically use 0.22 μm of membrane filtration degerming, obtain sea-mussel mucin solution for later use;
(4) gel preparation: aseptically the product of step (2) and step (3) is fully mixed, the antipruritic sea-mussel mucin gel of obtained reparation.
Further, in step (1), stirring with pH value regulator adjustment solution pH value is 4.8, at 0.12MPa pressure, under 125 DEG C of conditions, and 30min autoclaving, for subsequent use after cooling.
The application of reparation of the present invention antipruritic sea-mussel mucin gel in the middle of the antipruritic treatment of wound repair.
Beneficial effect: the present invention has good bioadhesive, effectively adhere to wound surface fast, rapid antipruritic pain relieving, has reduced immunogenicity, good, easy to use with the human-body biological compatibility, do not cause allergy, toleration strong, without skin irritation, safety non-toxic, have no adverse reaction.Compensate for spray type deficiency, meet more clinical practice demand, can long period and site of action generation close contact, jointly can use with other products.Sea-mussel mucin is made gel, stable in properties, degradation cycle is long, can play the effect of Promotive union, antipruritic pain relieving lastingly.
(1) sea-mussel mucin have reduced immunogenicity, with the human-body biological compatibility good, do not cause allergy, without skin irritation.Micromolecule aminoacid is resolved into, safe, nontoxic, no dependence and toleration after degraded.Be applicable to the special population that all security requirements are high.Sea-mussel mucin coagulates the gel efficacy and safety made and is better than other conventional exterior-applied formulations.
(2) deficiency of local unguentum poor permeability is overcome; and activated protein preparation after treatment overcomes needs lyophilization could stablize the defect of preserving; acid is planted for protein protective agent with natural origin; be conducive to the maintenance of protein stabilized environment; and the material that phytic acid is inherently useful to human body, the phospholipid produced after decomposing is the important component part of human body cell.Enrich form of administration, meet the medication demand of extensive patients.
Detailed description of the invention
Further specific descriptions will be done by specific embodiment to the present invention below, but can not be interpreted as it is limiting the scope of the present invention.
The invention provides the antipruritic sea-mussel mucin gel of a kind of reparation, described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
The pH value of the antipruritic sea-mussel mucin gel of described reparation is 3.8-5.8.
Described high-molecular matrix material is the combination of one or more in Carbomer-940, hydroxypropyl emthylcellulose, methylcellulose, hydroxy methocel.
Described wetting agent is the combination of one or more in glycerol, ethylene glycol, sorbitol, glycerol.
Described surfactant is that Tween 80, fatty acid Pyrusussuriensis are smooth, the combination of one or more in dodecyl sodium sulfate.
Described antiseptic is nipagin A; Described stabilizing agent is the combination of one or more in low molecular dextran, ethylenediaminetetraacetic acid, disodiumedetate, sodium ethylene diamine tetracetate calcium.
Described antibacterial is the combination of one or more in nipagin A, dimethyl fumarate, low-grade fatty acid ester; Described PH regulator is the combination of one or more in citric acid, sorbic acid, sodium sesquicarbonate.
The preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprises the steps:
(1) utensil prepares: just all utensils are cleaned, sterilizing;
(2) the swelling and sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 3.8-5.8, at 0.1-0.15MPa pressure, under 120-130 DEG C of condition, 30min autoclaving, for subsequent use after cooling;
(3) albumen aseptic filtration: the protein protective agent of 1%-2% in sea-mussel mucin raw material feed liquid after treatment, then the 1%-2% of original concentration is diluted to by purified water, aseptically use 0.22 μm of membrane filtration degerming, obtain sea-mussel mucin solution for later use;
(4) gel preparation: aseptically the product of step (2) and step (3) is fully mixed, the antipruritic sea-mussel mucin gel of obtained reparation.
The application of reparation of the present invention antipruritic sea-mussel mucin gel in the middle of the antipruritic treatment of wound repair.
The present invention has good bioadhesive, effectively adheres to wound surface fast, and rapid antipruritic pain relieving, has reduced immunogenicity, good, easy to use with the human-body biological compatibility, do not cause allergy, toleration strong, without skin irritation, safety non-toxic, have no adverse reaction.Compensate for spray type deficiency, meet more clinical practice demand, can long period and site of action generation close contact, jointly can use with other products.Sea-mussel mucin is made gel, stable in properties, degradation cycle is long, can play the effect of Promotive union, antipruritic pain relieving lastingly.
(1) sea-mussel mucin have reduced immunogenicity, with the human-body biological compatibility good, do not cause allergy, without skin irritation.Micromolecule aminoacid is resolved into, safe, nontoxic, no dependence and toleration after degraded.Be applicable to the special population that all security requirements are high.Sea-mussel mucin coagulates the gel efficacy and safety made and is better than other conventional exterior-applied formulations.
(2) deficiency of local unguentum poor permeability is overcome; and activated protein preparation after treatment overcomes needs lyophilization could stablize the defect of preserving; acid is planted for protein protective agent with natural origin; be conducive to the maintenance of protein stabilized environment; and the material that phytic acid is inherently useful to human body, the phospholipid produced after decomposing is the important component part of human body cell.Enrich form of administration, meet the medication demand of extensive patients.
Embodiment 1
Produce 5000g and repair antipruritic sea-mussel mucin gel, described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
The pH value of the antipruritic sea-mussel mucin gel of described reparation is 3.8.
Described high-molecular matrix material is Carbomer-940 and hydroxypropyl emthylcellulose.
Described wetting agent is glycerol and ethylene glycol.
Described surfactant is Tween 80.
Described antiseptic is nipagin A; Described stabilizing agent is low molecular dextran and ethylenediaminetetraacetic acid.
Described antibacterial is nipagin A and dimethyl fumarate; Described PH regulator is citric acid, sorbic acid, sodium sesquicarbonate.
The preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprises the steps:
(1) utensil prepares: just all utensils are cleaned, sterilizing;
(2) the swelling and sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 3.8, at 0.1MPa pressure, under 120 DEG C of conditions, 30min autoclaving, for subsequent use after cooling;
(3) albumen aseptic filtration: in sea-mussel mucin raw material feed liquid after treatment 1% protein protective agent, then 1% of original concentration is diluted to by purified water, aseptically use 0.22 μm of membrane filtration degerming, obtain sea-mussel mucin solution for later use;
(4) gel preparation: aseptically the product of step (2) and step (3) is fully mixed, the antipruritic sea-mussel mucin gel of obtained reparation.
The application of reparation of the present invention antipruritic sea-mussel mucin gel in the antipruritic material of wound repair.
Embodiment 2
Embodiment 2 is with the difference of embodiment 1: produce 5000g and repair antipruritic sea-mussel mucin gel, described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
The pH value of the antipruritic sea-mussel mucin gel of described reparation is 5.8.
Described high-molecular matrix material is methylcellulose and hydroxy methocel.Described wetting agent is sorbitol and glycerol.Described surfactant is the smooth and dodecyl sodium sulfate of fatty acid Pyrusussuriensis.Described stabilizing agent is disodiumedetate and sodium ethylene diamine tetracetate calcium.Described antibacterial is low-grade fatty acid ester; Described PH regulator is citric acid.
The preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprises the steps: the preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprises the steps:
In step (2), swelling and the sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 5.8, at 0.15MPa pressure, under 130 DEG C of conditions, 30min autoclaving, for subsequent use after cooling.
Embodiment 3
Embodiment 3 is with the difference of embodiment 1: produce 5000g and repair antipruritic sea-mussel mucin gel, and the invention provides the antipruritic sea-mussel mucin gel of a kind of reparation, described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
The pH value of the antipruritic sea-mussel mucin gel of described reparation is 4.2.
Described high-molecular matrix material is hydroxy methocel.Described wetting agent is glycerol.Described surfactant is dodecyl sodium sulfate.Described stabilizing agent is low molecular dextran, disodiumedetate and sodium ethylene diamine tetracetate calcium.
Described antibacterial is nipagin A and low-grade fatty acid ester; Described PH regulator is sodium sesquicarbonate.
The preparation method of the antipruritic sea-mussel mucin gel of reparation of the present invention, comprise the steps: in step (2), swelling and the sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 4.8, at 0.2MPa pressure, under 125 DEG C of conditions, 30min autoclaving, for subsequent use after cooling.
Test 1
Antipruritic experiment
Get Cavia porcellus 20 and be divided into two groups at random, often organize 10, male and female half and half, be respectively matrix group and repair antipruritic sea-mussel mucin gel.24h before experiment, shaves hair to each group of right back foot of Cavia porcellus, coating 1 time.Experiment same day, abrade right back foot with coarse sandpaper and shave hair place, coating is once again in area 1cm2. local, only wound surface Chu Di 0.01% histamine phosphate 0.05ml/ is started again after 10min, after this comply with 0.02%, 0.03% progressive concentration every 3min, be only 0.05ml/ at every turn.Until Cavia porcellus later lick right back sufficient time histamine phosphate's total amount (μ g) of giving for causing valve of itching.Record relatively each group cause valve of itching, result shows: repair antipruritic sea-mussel mucin gel group and cause valve of itching (348-400.2) μ g, compare with matrix group (47.2-55) μ g, P < 0.01 repairs the effect that antipruritic sea-mussel mucin gel has pruritus caused by significantly antagonism histamine phosphate as seen.
Wound healing is tested
Get Cavia porcellus 10, be divided into A group and B group two groups, often organize 5, by guinea pig back cropping, alcohol disinfecting, at the full thickness skin of back excision 2 × 2cm, antipruritic for reparation sea-mussel mucin gel is applied on wound surface by A group, and B smears substrate.Post operation is observed and is repaired antipruritic sea-mussel mucin gel to the reparation situation record wound healing time of wound surface for 1 day, 3 days, 5 days, 7 days, 14 days.(see table 1)
Within postoperative 14 days two, form a mouthful all healed, without swelling phenomenon.A group skin color is normal, has slight cicatrix.B group skin color is light rubescent, has larger cicatrix.A forms mouthful healing state and is obviously better than B group, and A group (sea-mussel mucin gel) sample has promotion wound healing, reduces effect of cicatrix.
More than show and describe ultimate principle of the present invention, principal character and advantage of the present invention.The technical staff of the industry should understand; the present invention is not restricted to the described embodiments; what describe in above-described embodiment and description just illustrates principle of the present invention; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and application claims protection domain is defined by appending claims, description and equivalent thereof.
Claims (10)
1. repair an antipruritic sea-mussel mucin gel, it is characterized in that: described reparation antipruritic sea-mussel mucin gel is composed of the following components by mass percentage:
2. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: the pH value of the antipruritic sea-mussel mucin gel of described reparation is 3.8-5.8.
3. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: described high-molecular matrix material is the combination of one or more in Carbomer-940, hydroxypropyl emthylcellulose, methylcellulose, hydroxy methocel.
4. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: described wetting agent is the combination of one or more in glycerol, ethylene glycol, sorbitol, glycerol.
5. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: described surfactant is that Tween 80, fatty acid Pyrusussuriensis are smooth, the combination of one or more in dodecyl sodium sulfate.
6. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: described antiseptic is nipagin A; Described stabilizing agent is the combination of one or more in low molecular dextran, ethylenediaminetetraacetic acid, disodiumedetate, sodium ethylene diamine tetracetate calcium.
7. the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that: described antibacterial is the combination of one or more in nipagin A, dimethyl fumarate, low-grade fatty acid ester; Described PH regulator is the combination of one or more in citric acid, sorbic acid, sodium sesquicarbonate.
8. the preparation method of the antipruritic sea-mussel mucin gel of reparation according to claim 1, is characterized in that comprising the steps:
(1) utensil prepares: just all utensils are cleaned, sterilizing;
(2) the swelling and sterilizing of substrate: take high-molecular matrix material, wetting agent, surfactant, antiseptic, stabilizing agent and antibacterial according to the ratio of above-mentioned mass percent, then after mixing, add the naturally swelling 24h of purified water, stirring with pH value regulator adjustment solution pH value is 3.8-5.8, at 0.1-0.15MPa pressure, under 120-130 DEG C of condition, 30min autoclaving, for subsequent use after cooling;
(3) albumen aseptic filtration: the protein protective agent of 1%-2% in sea-mussel mucin raw material feed liquid after treatment, then the 1%-2% of original concentration is diluted to by purified water, aseptically use 0.22 μm of membrane filtration degerming, obtain sea-mussel mucin solution for later use;
(4) gel preparation: aseptically the product of step (2) and step (3) is fully mixed, the antipruritic sea-mussel mucin gel of obtained reparation.
9. the preparation method of the antipruritic sea-mussel mucin gel of reparation according to claim 7, is characterized in that: in step (1), and stirring with pH value regulator adjustment solution pH value is 4.8, at 0.12MPa pressure, under 125 DEG C of conditions, 30min autoclaving, for subsequent use after cooling.
10. the application of reparation according to claim 1 antipruritic sea-mussel mucin gel in the middle of the antipruritic treatment of wound repair.
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