CN210992033U - Amnion or micro-droplet drug-loaded composite dressing - Google Patents
Amnion or micro-droplet drug-loaded composite dressing Download PDFInfo
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- CN210992033U CN210992033U CN201920744012.3U CN201920744012U CN210992033U CN 210992033 U CN210992033 U CN 210992033U CN 201920744012 U CN201920744012 U CN 201920744012U CN 210992033 U CN210992033 U CN 210992033U
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Abstract
The utility model discloses a compound dressing of amnion or micro-droplet package year medicine relates to the medicine field. The dressing is used for solving the problem that the cost is relatively high because the conventional dressing does not have self-adhesion and needs to be fixed by an auxiliary dressing. The amnion or micro-droplet drug-loaded composite dressing comprises: dressing, amnion, and water micro-droplet coated with slow-release medicine; the aqueous micro-droplets wrapping the slow-release drugs are adhered to the inner surface of the amnion; the amnion is adhered to the inner surface of the dressing through the water micro-droplets wrapping the slow-release drug.
Description
Technical Field
The utility model relates to the technical field of medicine, more specifically relates to a compound dressing of amnion or micro-droplet package year medicine.
Background
Medical dressings are medical materials that cover sores, wounds, or other lesions. With the intensive research on the pathophysiology of the wound healing process, people understand the wound healing process more and more deeply, thereby leading to the continuous improvement and development of medical dressings. Currently, alginate dressings are the most advanced medical dressings in the world. The main component of the alginate dressing is alginate, which is natural cellulose and has no toxicity to human body. After contacting wound exudate, soft gel can be formed, an ideal moist environment is provided for wound healing, wound healing is promoted, and wound pain is relieved; and release Ca2+It can promote the formation of prothrombin activator and accelerate the blood coagulation process. However, the disadvantages of this material are also evident: the adhesive tape does not have self-adhesion, and auxiliary dressing is needed for fixing; the cost is relatively high, and the burden of the patient is increased.
SUMMERY OF THE UTILITY MODEL
The embodiment of the utility model provides an amnion or compound dressing of micro-droplet package year medicine for solve current dressing because of do not possess the autohension, need supplementary dressing to fix, lead to the relatively higher problem of cost.
The embodiment of the utility model provides an amnion or little liquid drop package carry compound dressing of medicine, include: dressing, amnion, and water micro-droplet coated with slow-release medicine;
the aqueous micro-droplets wrapping the slow-release drugs are adhered to the inner surface of the amnion;
the amnion is adhered to the inner surface of the dressing through the water micro-droplets wrapping the slow-release drug.
Preferably, the diameter of the water micro-droplet for wrapping the slow-release medicine is 3 nm-7 nm.
Preferably, the diameter of the water micro-droplet wrapping the slow-release medicine is 5 nm.
Preferably, the size of the amniotic membrane is cut according to the area of use.
Preferably, the slow release medicament comprises one or more of the following in combination:
anti-inflammatory drugs, antibacterial drugs, and wound healing drugs.
Preferably, the amnion preservation solution comprises: 100% glycerol, 10 million units of gentamicin, 80 million units of penicillin, 50 million units of streptomycin and normal saline.
Preferably, the placenta comprises the placenta of a parturient, pig, cow, sheep mammal;
and when the puerpera, the pig, the cattle and the sheep are detected before delivery, the placenta donor hepatitis B surface antigen, the AIDS antigen, the chlamydia, the syphilis and the cytomegalovirus are negative.
The embodiment of the utility model provides a composite dressing of amnion or micro-droplet encapsulated drug, which comprises a dressing, amnion and water micro-droplet encapsulated slow-release drug; the aqueous micro-droplets wrapping the slow-release drugs are adhered to the inner surface of the amnion; the amnion is adhered to the inner surface of the dressing through the water micro-droplets wrapping the slow-release drug. The amnion or micro-droplet drug-loaded composite dressing has a sustained-release effect, can prolong the circulation time of the drug in vivo to achieve the effect of prevention and treatment; the water micro-droplets carrying the slow-release drugs are uniformly adhered to the inner surface of the amnion, so that a moist environment is provided for the wound, the exuded tissue fluid can be absorbed, and inflammation and wound fester are prevented; the formation of scars can be reduced by releasing the amnion component to the wound; the amnion or micro-droplet drug-loaded composite dressing does not use organic solvents such as chemical adhesives and the like in the bonding process, and the aqueous micro-droplet can be used as a carrier for slowly releasing drugs and can also be used as an adhesive, so that the problem that the dressing in the prior art does not have self-adhesion and needs to be fixed by an auxiliary dressing, which causes relatively high cost is solved.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only some embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to these drawings without creative efforts.
Fig. 1 is a schematic structural view of a composite dressing for encapsulating a drug in amnion or micro-droplet according to an embodiment of the present invention;
fig. 2 is a schematic flow chart of a method for preparing a composite dressing for encapsulating a drug in amnion or micro-droplet according to an embodiment of the present invention;
fig. 3 is a schematic view of wound healing and scar reduction of a mouse for treating chronic ulcer according to an embodiment of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention will be described clearly and completely with reference to the accompanying drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only some embodiments of the present invention, not all embodiments. Based on the embodiments in the present invention, all other embodiments obtained by a person skilled in the art without creative work belong to the protection scope of the present invention.
Fig. 1 is a schematic structural view of a composite dressing for amnion or micro-droplet drug-loading provided by an embodiment of the present invention, as shown in fig. 1, the composite dressing for amnion or micro-droplet drug-loading mainly includes: dressing 1, amnion 2 and water micro-drop 3 wrapping the slow-release medicine.
Specifically, the aqueous micro-droplets 3 wrapping the sustained-release drug are adhered to the inner surface of the amnion 2, and in practical application, in order to improve the adhesion degree between the aqueous micro-droplets 3 wrapping the sustained-release drug and the amnion 2, preferably, the aqueous micro-droplets 3 wrapping the sustained-release drug are uniformly adhered to the inner surface of the amnion 2; further, the amnion 2 is adhered to the inner surface of the dressing 1 by the micro-drop 3 of the water and water coated with the slow release medicine, similarly, in order to improve the adhesion degree of the amnion 2 and the dressing 1, the micro-drop 3 of the water and water coated with the slow release medicine is preferably adhered to the inner surface of the dressing 1 uniformly. Here, it can be understood that the inner surface of the amnion 2 and the inner surface of the dressing 1 are uniformly adhered by the water micro-droplets 3 coated with the sustained-release drug.
The amnion or micro-droplet drug-encapsulated composite dressing provided by the embodiment of the utility model comprises slow-release drugs, thereby achieving the effect of prevention and treatment. Further, in order to solve the problem that the dressing 1 does not have self-adhesion in the prior art, the dressing 1 needs to be fixed, which results in relatively high cost. Preferably, in the embodiment of the present invention, because the surface area of the water micro-droplet 3 coated with the slow-release drug is larger than the surface area in the amniotic membrane, and the water micro-droplet 3 coated with the slow-release drug and arranged on the inner surface of the amniotic membrane 2 is a drug-carrying container, the drug-carrying amount can be increased, the circulation time of the drug in vivo to exert the drug effect can be prolonged, and the effect of prevention and treatment can be finally achieved; furthermore, the aqueous micro-droplets 3 wrapping the slow-release drugs can also be used as an adhesive to adhere the inner surface of the amnion 2 and the inner surface of the dressing 1, and the aqueous micro-droplets 3 wrapping the slow-release drugs can provide a moist environment for the wound to absorb exuded tissue fluid, so that the effects of preventing inflammation and wound ulceration can be achieved.
The aqueous micro-droplet 3 for wrapping the sustained-release drug provided in the amnion or micro-droplet drug-loaded composite dressing is obtained by reacting the first aqueous micro-droplet with sustained-release requirements according to a certain mass ratio. Specifically, the first water micro-droplet and the sustained-release drug may be mixed at a mass ratio of 25:1, to prepare the water micro-droplet 3 for wrapping the slow-release medicine. In practical applications, the diameter of the first water micro-droplets is between 3nm and 7nm, and preferably, the diameter of the first water micro-droplets is 5 nm. Correspondingly, the diameter of the water micro-droplet 3 for wrapping the slow release medicine is also between 3nm and 7nm, and preferably, the diameter of the water micro-droplet 3 for wrapping the slow release medicine is 5 nm.
Further, the slow-release medicine in the water micro-droplet 3 wrapping the slow-release medicine mainly comprises one or more of the following combinations: anti-inflammatory drugs, antibacterial drugs, and wound healing drugs. In the embodiment of the present invention, the specific type of the sustained-release drug is not limited.
In order to promote wound healing and reduce scar formation, the defect that the existing therapy is not suitable for large-area wounds and is easy to generate scars is overcome, and the application value of the traditional Chinese medicine composition is wide in treatment of large-area wounds, operation wounds, chemical burns, wounds which are difficult to heal and caused by chronic diseases and the like. The embodiment of the utility model provides an aspect provides the amnion 2 from the placenta, and on the other hand will come from the amnion 2 of placenta and combine to use with the slowly-releasing medicine to can wound healing and reduce the formation of scar, reduced the formation of scar.
In the embodiment of the present invention, before preparing the amnion into the amnion or the compound dressing with the microdroplet carrying the drug, vacuum treatment is performed, and the amnion after vacuum treatment is stored at a temperature of 22-28 ℃. The amnion or micro-droplet drug-loaded composite dressing is dried by nitrogen and sterilized by radiation, so that the amnion or micro-droplet drug-loaded composite dressing is obtained, and after the amnion or micro-droplet drug-loaded composite dressing is obtained, the amnion or micro-droplet drug-loaded composite dressing needs to be stored at the temperature of 22-28 ℃.
In the embodiment of the present invention, the amnion 2 can be designed or cut according to the size of the wound of the patient to be used before being prepared into the amnion or micro-droplet drug-loaded composite dressing.
In the embodiment of the utility model, the amnion 2 preservation solution mainly comprises 100% glycerol, 10 ten thousand units of gentamicin, 80 ten thousand units of penicillin, 50 ten thousand units of streptomycin and normal saline.
To sum up, the embodiment of the utility model provides an amnion or micro-droplet drug-loaded composite dressing, the amnion or micro-droplet drug-loaded composite dressing has a slow release effect, can prolong the drug in vivo drug effect cycle time, and finally achieves the effect of prevention and treatment; the water micro-droplets carrying the slow-release drugs are uniformly adhered to the inner surface of the amnion, so that a moist environment is provided for the wound, the exuded tissue fluid can be absorbed, and inflammation and wound fester are prevented; the formation of scars can be reduced by releasing the amnion component to the wound; the amnion or micro-droplet drug-loaded composite dressing does not use organic solvents such as chemical adhesives and the like in the bonding process, and the aqueous micro-droplet can be used as a carrier for slowly releasing drugs and can also be used as an adhesive, so that the problem that the dressing in the prior art does not have self-adhesion and needs to be fixed by an auxiliary dressing, which causes relatively high cost is solved.
In order to introduce the composite dressing of the amnion or the micro-droplet encapsulated drug more clearly, the embodiment of the utility model also provides a preparation method of the composite dressing of the amnion or the micro-droplet encapsulated drug, the following embodiment combines the flow schematic diagram of the composite dressing of the amnion or the micro-droplet encapsulated drug provided by fig. 2, and introduces the preparation method of the composite dressing of the amnion or the micro-droplet encapsulated drug in detail, as shown in fig. 2, the preparation method of the composite dressing of the amnion or the micro-droplet encapsulated drug comprises the following steps:
example one
102, dissolving a first water micro-droplet with the mass of 20-25 mg and a sustained-release drug with the mass of 0.5-1.0 mg in an aqueous solution C with the volume of 8-10 ml according to the mass ratio of 25:1, and reacting for 4-6 h at a second set temperature and a second set rotating speed to obtain a water micro-droplet wrapping the sustained-release drug;
103, soaking the placenta for 30min by using an amnion preservation solution containing gentamicin, streptomycin, penicillin and physiological saline, separating chorion of the placenta after washing, paving the upper surface of the separated placenta on surgical adhesive paper, soaking the placenta in physiological saline containing antibiotics for 30min to obtain amnion, and performing vacuum treatment on the amnion and preserving the amnion at the temperature of 22-28 ℃;
104, soaking the amnion in a 24-hole plate containing the solution of the water micro-droplet coated with the slow-release medicament, cleaning the amnion with ultrapure water after soaking for 2 hours, and drying the amnion by adopting nitrogen to obtain the composite dressing of the amnion or the micro-droplet coated medicament; or spraying the solution of the water micro-droplets coating the slow-release drugs on the inner surface of the amnion, drying by using nitrogen and sterilizing by radiation to obtain the amnion or micro-droplet drug-coated composite dressing, wherein the amnion or micro-droplet drug-coated composite dressing is stored at the temperature of 22-28 ℃, and the radiation comprises electron beam radiation, gamma ray radiation and/or ultraviolet radiation.
In step 101, adding an aqueous solution A containing dextran, trehalose and gelatin into an aqueous solution B containing polyethylene glycol to form a fibril network, further adding egg white lysozyme with the mass percentage concentration of 0.5-1.0 wt% into the fibril network, and reacting for 10-12 h at a first set temperature and a first set rotation speed to obtain first water micro-droplets.
The aqueous solution A comprises dextran with the percentage concentration of 1.0-1.5 wt%, trehalose with the percentage concentration of 0.1-0.5 wt%, gelatin with the percentage concentration of 0.1-0.5 wt%, and the aqueous solution B comprises polyethylene glycol with the mass percentage concentration of 5.5-6.5 wt%.
Further, the first set temperature is 60 ℃, the first set rotation speed is between 100rpm (revolutions per minute) and 200rpm, the diameter of the formed first water micro-droplets is between 3nm and 7nm, and preferably, the diameter of the first water micro-droplets is 5 nm.
In step 102, dissolving the first aqueous micro-droplet with the mass of 20mg to 25mg and the sustained-release drug with the mass of 0.5mg to 1.0mg in the aqueous solution C with the volume of 8ml to 10ml according to the mass ratio of 25:1, and reacting for 4h to 6h at a second set temperature and a second set rotation speed, so as to obtain the aqueous micro-droplet coated with the sustained-release drug.
In the embodiment of the present invention, the slow-release drug includes one or more of the following combinations: anti-inflammatory drugs, antibacterial drugs, wound healing drugs, and the like.
It should be noted that the second set temperature is 0-4 ℃, the second set rotation speed is 230-260 rpm, the diameter of the formed water micro-droplet for wrapping the sustained-release drug is 3-7 nm, and preferably, the diameter of the water micro-droplet for wrapping the sustained-release drug is 5 nm.
In step 103, the amniotic membrane preservation solution comprises 100% glycerol, 10 ten thousand units of gentamicin, 80 ten thousand units of penicillin, 50 ten thousand units of streptomycin and physiological saline.
The amnion selected in this step is derived from placenta, which includes placenta of high-grade mammals such as healthy parturient, pig, cow, sheep, etc. Furthermore, the placenta of lying-in women, pigs, cattle and sheep is detected before delivery, and the detection items comprise hepatitis B surface antigen, AIDS antigen, chlamydia, syphilis and cytomegalovirus. It should be noted that the placenta selected in the embodiment of the present invention is negative in the detection items, and the above-mentioned high-grade animals such as puerpera, pig, cow, sheep, etc. have no history of other malignant tumors and infectious diseases.
The amnion is obtained by soaking the placenta in an amnion preservation solution for 30min when the amnion is obtained from the placenta, and washing for multiple times after soaking until blood stains in the placenta are cleaned.
In practical applications, the amnion is stored after it is harvested. In the embodiment of the present invention, the obtained amnion is subjected to vacuum treatment, and then the amnion after the vacuum treatment is stored at room temperature, and in the embodiment of the present invention, the room temperature may be between 22 ℃ and 28 ℃. In practical applications, the temperature for cryopreservation may be 22 °, 28 °, or 25 °. In the embodiments of the present invention, the specific temperature of the room temperature is not limited.
In step 104, soaking the amnion in a 24-hole plate containing water micro-droplets wrapping the slow-release drug, cleaning the amnion with ultrapure water for 3-5 times after soaking for 1-3 h, 3min each time, and finally drying the amnion with nitrogen to obtain the composite dressing of the amnion or the micro-droplets wrapping the drug;
the embodiment of the utility model provides an in still provide another preparation method, specifically, after will wrap up the solution of the water micro-droplet of slowly-releasing medicine spraying at the internal surface of amnion, then adopt nitrogen gas drying and radiation sterilization, obtain amnion or micro-droplet and carry compound dressing of medicine at last.
In this step, the radiation sterilization may be electron beam radiation, may be gamma ray radiation, and may also be ultraviolet radiation. In the embodiments of the present invention, the specific form of radiation sterilization is not limited.
It should be noted that, after the amnion or micro-droplet drug-loaded composite dressing is prepared through the above steps 101 to 104, the amnion or micro-droplet drug-loaded composite dressing needs to be preserved, in the embodiment of the present invention, the preservation method of the amnion or micro-droplet drug-loaded composite dressing is the same as the preservation method of the amnion, and both the preservation methods can be performed at room temperature, where the room temperature can be between 22 ℃ and 28 ℃.
To sum up, the embodiment of the utility model provides a preparation method of amnion or micro-droplet drug-loaded composite dressing, amnion or micro-droplet drug-loaded composite dressing's preparation method through this method preparation can solve current dressing because of not possessing the autohension, need supplementary dressing to fix, lead to the problem that the cost is relatively higher.
In practical application, because various substances involved in preparing the amnion or micro-droplet drug-loaded composite dressing correspond to different percentage concentrations, the preparation method of the amnion or micro-droplet drug-loaded composite dressing is described in detail below by taking the first to twenty embodiments as examples.
Example two
Step 201, adding dextran, trehalose and gelatin solutions with mass percentage concentrations of 1.5 wt%, 0.5 wt% and 0.5 wt% respectively into polyethylene glycol solution with mass percentage concentration of 6.5 wt% to form fibril network, then adding 1 wt% egg white lysozyme, and reacting for 10 hours at the temperature of 60 ℃ and under the condition that the rotating speed is 100rpm, thereby forming first water micro-droplets with the diameter of 5 nm.
Step 202, dissolving 25mg of first water micro-droplets and the sustained-release drug in 10ml of aqueous solution according to the mass ratio of 25:1, and reacting for 5 hours at the temperature of 4 ℃ and the rotation speed of 250rpm to finally obtain the water micro-droplets wrapping the sustained-release drug.
Step 203, soaking the placenta for 30min by using an amniotic membrane preservation solution containing penicillin, streptomycin, penicillin and normal saline, washing for a plurality of times until blood stains on the placenta are washed out, then carrying out blunt separation on the amniotic membrane from the chorion of the placenta, flatly paving the classified upper surface of the amniotic membrane on surgical adhesive paper, and soaking the surgical adhesive paper adhered with the amniotic membrane in the normal saline containing antibiotics for 30min to obtain the amniotic membrane.
Step 204, soaking the amnion in a 24-hole plate containing a water-water micro-droplet solution wrapping the slow-release drug, cleaning the amnion for 3 times with ultrapure water after soaking for 2 hours, wherein each time lasts for 3min, and then drying the amnion with nitrogen to obtain the amnion or the micro-droplet drug-wrapped composite dressing.
Or spraying the solution of the water micro-droplets for wrapping the slow-release medicament on the inner surface of the amnion, and drying by adopting nitrogen to obtain the amnion or the amnion with the micro-droplets for wrapping the medicament or the compound dressing with the micro-droplets for wrapping the medicament.
It should be noted that, after the amnion or micro-droplet drug-loaded composite dressing is prepared through the above steps 201 to 204, the amnion or micro-droplet drug-loaded composite dressing needs to be preserved, in the embodiment of the present invention, the preservation method of the amnion or micro-droplet drug-loaded composite dressing is the same as the preservation method of the amnion, and both the preservation methods can be performed at room temperature, where the room temperature can be between 22 ℃ and 28 ℃.
In the embodiment of the utility model, the preparation of the amnion or the compound dressing of the micro-droplet encapsulated drug comprises 4 steps of the preparation of the first water micro-droplet, the preparation of the water micro-droplet encapsulated slow-release drug, the obtaining of the amnion, the adhesion of the water micro-droplet encapsulated drug on the inner surface of the amnion, and the like. In practical application, the preparation of the amnion or the compound dressing of the micro-droplet drug-loaded can only modify one step, the rest steps are not changed, and the amnion artificial lens with better quality and performance can be prepared. In the following examples three to twelve, since the material composition of the first water micro droplets is changed, the step of preparing the first water as droplets will be described in detail, and the other preparation steps are not changed, so that only the preparation of the first water micro droplets is described in the following examples three to twelve, and the other steps can be referred to as example one or example two.
EXAMPLE III
Step 301 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.0 wt%, 0.1 wt% and 0.1 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 5.5 wt% to form a fibril network, adding egg white lysozyme with the mass percentage concentration of 0.5 wt%, and reacting for 12 hours at the temperature of 65 ℃ and the rotation speed of 200rpm to obtain first water micro-droplets with the diameter of 5 nm.
Example four
Step 401 preparation of first aqueous micro droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.3 wt%, 0.3 wt% and 0.3 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 6.0 wt% to form a fibril network, adding 0.8 wt% of egg white lysozyme, and reacting for 11 hours at the temperature of 63 ℃ and the rotation speed of 150rpm to prepare the first aqueous micro-droplet with the diameter of 5 nm.
EXAMPLE five
Step 501 preparation of first water micro-droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.5 wt%, 0.5 wt% and 0.5 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 6.5 wt% to form a fibril network, adding egg white lysozyme with the mass percentage of 1.0 wt%, and reacting for 10 hours at the temperature of 60 ℃ and the rotation speed of 100rpm to prepare the first water micro-droplet with the diameter of 5 nm.
EXAMPLE six
Step 501 preparation of first water micro-droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.0 wt%, 0.1 wt% and 0.1 wt% respectively into a solution containing polyethylene glycol with the mass percentage concentration of 6.0 wt% to form a fibril network, then adding 0.5 wt% of egg white lysozyme, and reacting for 12 hours at the temperature of 65 ℃ and the rotation speed of 200rpm to prepare the first aqueous micro-droplet with the diameter of 5 nm.
EXAMPLE seven
Step 701 preparation of first aqueous micro droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.0 wt%, 0.1 wt% and 0.1 wt% respectively into a solution containing polyethylene glycol with the mass percentage concentration of 6.0 wt% to form a fibril network, then adding 0.8 wt% of egg white lysozyme, and reacting for 12 hours at the temperature of 65 ℃ and the rotation speed of 200rpm to prepare the first aqueous micro-droplet with the diameter of 5 nm.
Example eight
Step 801 preparation of first aqueous micro droplets: adding dextran, trehalose and gelatin with the mass percent concentration of 1.0 wt%, 0.1 wt% and 0.1 wt% respectively into a solution containing polyethylene glycol with the mass percent concentration of 6.0 wt% to form a fibril network, adding 0.8 wt% of egg white lysozyme, and reacting for 11 hours at the temperature of 63 ℃ and the rotation speed of 150rpm to prepare the first aqueous micro-droplet with the diameter of 5 nm.
Example nine
Step 901 preparation of first aqueous micro droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.3 wt%, 0.3 wt% and 0.3 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 5.5 wt% to form a fibril network, adding 0.8 wt% of egg white lysozyme, and reacting for 11 hours at the temperature of 63 ℃ and the rotation speed of 150rpm to prepare the first water micro-droplet with the diameter of 5 nm.
Example ten
Step 1001 preparation of first aqueous micro droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.3 wt%, 0.3 wt% and 0.3 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 5.5 wt% to form a fibril network, adding 0.8 wt% of egg white lysozyme, and reacting for 10 hours at the temperature of 60 ℃ and the rotation speed of 100rpm to prepare the first water micro-droplet with the diameter of 5 nm.
EXAMPLE eleven
Step 1101 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.5 wt%, 0.5 wt% and 0.5 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 6.0 wt% to form a fibril network, adding egg white lysozyme with the mass percentage of 1.0 wt%, and reacting for 11 hours at the temperature of 63 ℃ and the rotation speed of 150rpm to prepare the first water micro-droplet with the diameter of 5 nm.
Example twelve
Step 1201 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin with the mass percentage concentration of 1.5 wt%, 0.5 wt% and 0.5 wt% into a solution containing polyethylene glycol with the mass percentage concentration of 5.5 wt% to form a fibril network, adding egg white lysozyme with the mass percentage of 1.0 wt%, and reacting for 11 hours at the temperature of 63 ℃ and the rotation speed of 150rpm to prepare the first water micro-droplet with the diameter of 5 nm.
In the following thirteen to twenty-one examples, the preparation method of the aqueous micro-droplets encapsulating the sustained-release drug is changed, and the remaining steps are not changed, so that only the preparation of the aqueous micro-droplets encapsulating the sustained-release drug is described in the following examples, and other steps can refer to the first or second example.
EXAMPLE thirteen
Step 1302, preparation of aqueous microdroplets encapsulating the sustained release drug: dissolving 20mg of the first water micro-droplet and 0.5mg of the sustained-release drug in 8ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 4h at 0 ℃ and the rotation speed of 230rpm to prepare the water micro-droplet coated with the sustained-release drug.
In order to further explain the water micro-droplet for wrapping the slow-release medicine provided by the embodiment of the utility model, the drug loading capacity and the long slow-release time are increased. Preferably, the aqueous micro-droplets encapsulating the sustained-release drug are sealed in a dialysis bag, and then placed in 10ml of PBS buffer, 0.5ml of the release substance is taken after 10 days, 20 days, 30 days, 40 days, 50 days and 60 days at 37 ℃ and 250rpm, and is supplemented with 0.5ml of PBS buffer, the solution is diluted 100 times, and the concentration percentage of the sustained-release drug in the dilution is determined, and the results are shown in Table I.
Example fourteen
Step 1402 preparation of aqueous micro-droplets encapsulating the sustained release drug: dissolving 20mg of the first water micro-droplet and 0.5mg of the sustained-release drug in 9ml of aqueous solution C according to the mass ratio of 25:1, and reacting for 4h at 0 ℃ and the rotation speed of 230rpm to prepare the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example fifteen
Step 1502 preparation of aqueous microdroplets encapsulating the sustained-release drug: dissolving 20mg of the first water micro-droplet and 0.5mg of the sustained-release drug in 10ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 4h at 0 ℃ and the rotation speed of 230rpm to prepare the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example sixteen
Step 1602 preparation of aqueous micro-droplets encapsulating the sustained-release drug: dissolving 2mg3 of the first water micro-droplet and 0.8mg of the sustained-release drug in 8ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 5h at 2 ℃ and the rotation speed of 250rpm to prepare the water micro-droplet wrapping the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example seventeen
Step 1702 preparation of aqueous microdroplets encapsulating the sustained release drug: dissolving 23mg of the first water micro-droplet and 0.8mg of the sustained-release drug in 9ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 5h at the temperature of 2 ℃ and the rotating speed of 250rpm to prepare the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
EXAMPLE eighteen
Step 1802, preparation of aqueous micro-droplets encapsulating the sustained-release drug: dissolving 23mg of the first water micro-droplet and 0.8mg of the sustained-release drug in 10ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 5h at the temperature of 2 ℃ and the rotating speed of 250rpm to prepare the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example nineteen
Step 1902 preparation of aqueous microdroplets encapsulating the sustained release drug: dissolving 2mg5 of the first water micro-droplet and 1.0mg of the sustained-release drug in 8ml of the aqueous solution C according to the mass ratio of 25:1, and reacting for 4h at 4 ℃ and the rotation speed of 250rpm to prepare the water micro-droplet wrapping the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example twenty
Step 2002 preparation of water micro-droplets wrapping the sustained-release drug: dissolving 25mg of first water micro-droplet and 1.0mg of sustained-release drug in 9ml of aqueous solution C according to the mass ratio of 25:1, and reacting for 5h at 4 ℃ and the rotation speed of 250rpm to obtain the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
Example twenty one
Step 2102 preparation of aqueous microdroplets encapsulating the sustained release drug: dissolving 25mg of first water micro-droplet and 1.0mg of sustained-release drug in 10ml of aqueous solution C according to the mass ratio of 25:1, and reacting for 6h at 4 ℃ and the rotation speed of 250rpm to obtain the water micro-droplet coated with the sustained-release drug.
The detection method is as in example thirteen, and the results are shown in table one.
TABLE I concentration percent of aqueous microdroplets encapsulating the sustained release drug
In the embodiment of the utility model, the preparation of the amnion or the compound dressing of the micro-droplet encapsulated drug comprises 4 steps of the preparation of the first water micro-droplet, the preparation of the water micro-droplet encapsulated slow-release drug, the obtaining of the amnion, the adhesion of the water micro-droplet encapsulated drug on the inner surface of the amnion, and the like.
In practical application, the obtaining of the amnion can comprise obtaining from placenta and artificially synthesizing, and the two modes of adhering the water micro-droplet coated with the drug on the inner surface of the amnion also comprise adhering the amnion by a soaking method and the water micro-droplet coated with the slow-release drug and spraying the solution of the water micro-droplet coated with the slow-release drug on the inner surface of the amnion, respectively aiming at the preparation methods, twenty-two to twenty-five embodiments are provided, the in-vitro release is determined by a dialysis bag method, the amnion or the compound dressing of the micro-droplet coated with the drug prepared in the twenty-two to twenty-five embodiments and the common dressing are put into a dialysis bag and sealed in 10ml PBS buffer solution, 0.5ml of release substances are respectively taken at 37 ℃, 250rpm, 5 days, 10 days, 20 days, 30 days, 40 days, 50 days and 60 days, 0.5ml of PBS buffer solution is respectively supplemented, the taken solution is diluted by 100 times, the anti-inflammatory drug concentration in the dilutions was determined and the detailed results are presented in the anti-inflammatory drug concentration table provided in table two.
Example twenty two
The preparation method of the compound dressing of amnion or micro-droplet encapsulated drug, the compound dressing is prepared by bonding amnion and water micro-droplet encapsulated slow-release drug by soaking method, the amnion is obtained from placenta, and the method specifically comprises the following steps:
step 2201 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin solutions with mass percentage concentrations of 1.5 wt%, 0.5 wt% and 0.5 wt% into a polyethylene glycol solution with mass percentage concentration of 6.5 wt% to form a fibril network, adding 1 wt% of egg white lysozyme, and reacting for 10 hours at the temperature of 60 ℃ and the rotation speed of 100rpm to form first water micro-droplets with the diameter of 5 nm;
step 2202 preparation of aqueous micro-droplets encapsulating the drug: dissolving 25mg of first water micro-droplets and the sustained-release drug in 10ml of aqueous solution according to the mass ratio of 25:1, and reacting for 5 hours at the temperature of 4 ℃ and the rotation speed of 250rpm to obtain drug-coated water micro-droplets;
2203, obtaining the amnion, namely soaking the placenta, which is produced by the cesarean section of a healthy lying-in woman, in an amnion preservation solution containing penicillin, streptomycin, penicillin and normal saline for 30min, washing for a plurality of times until the bloodstains on the placenta are washed, then performing blunt separation on the amnion from the chorion of the placenta, flatly paving the upper surface of the classified amnion on surgical adhesive paper, and soaking the surgical adhesive paper adhered with the amnion in the normal saline containing antibiotics for 30min to obtain the amnion, wherein the size of the amnion is 2cm × 4cm slices;
step 2204, adhering the micro-droplets of the water solution wrapping the medicine on the inner surface of the amnion: soaking amnion in 24-pore plate containing water micro-droplet solution for coating slow-release drug, cleaning with ultrapure water for 3 times (each time for 3 min) after soaking for 2h, and drying with nitrogen to obtain amnion or micro-droplet drug-loaded composite dressing.
Example twenty three
The amnion/micro-droplet drug-loaded composite dressing is prepared by spraying water micro-droplets on the inner surface of the amnion, wherein the amnion is artificially synthesized, and the preparation method comprises the following steps:
step 2301 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin solutions with mass percentage concentrations of 1.5 wt%, 0.5 wt% and 0.5 wt% into a polyethylene glycol solution with mass percentage concentration of 6.5 wt% to form a fibril network, adding 1 wt% of egg white lysozyme, and reacting at 60 ℃ and 100rpm for 10 hours to form first water micro-droplets with the diameter of 5 nm;
step 2302 preparation of aqueous microdroplets encapsulating a drug: dissolving 25mg of first water micro-droplets and the sustained-release drug in 10ml of aqueous solution according to the mass ratio of 25:1, and reacting for 5 hours at the temperature of 4 ℃ and the rotation speed of 250rpm to obtain drug-coated water micro-droplets;
step 2303, obtaining the amniotic membrane: artificially synthesizing an amnion;
2304 adhering the micro-droplet of water solution coated with the drug to the inner surface of amnion: spraying the solution of the water micro-droplets wrapping the slow-release medicament on the inner surface of the amnion by using a spraying instrument, and drying by using nitrogen to obtain the amnion or the compound dressing of the micro-droplets wrapping the medicament;
example twenty-four
The amnion/micro-droplet drug-loaded composite dressing is realized by bonding amnion and water micro-droplet by soaking method, the amnion is artificially synthesized, and the preparation method comprises the following steps:
step 2401, preparing a first aqueous micro-droplet: adding dextran, trehalose and gelatin solutions with mass percentage concentrations of 1.5 wt%, 0.5 wt% and 0.5 wt% into a polyethylene glycol solution with mass percentage concentration of 6.5 wt% to form a fibril network, adding 1 wt% of egg white lysozyme, and reacting for 10 hours at the temperature of 60 ℃ and the rotation speed of 100rpm to form first water micro-droplets with the diameter of 5 nm;
step 2402, preparing water-in-water micro-droplets wrapping the medicine: dissolving 25mg of first water micro-droplets and the sustained-release drug in 10ml of aqueous solution according to the mass ratio of 25:1, and reacting for 5 hours at the temperature of 4 ℃ and the rotation speed of 250rpm to obtain drug-coated water micro-droplets;
step 2403, obtaining the amnion: artificially synthesizing an amnion;
2405, adhering the water micro-droplets wrapping the medicine on the inner surface of the amnion: soaking amnion in 24-pore plate containing water micro-droplet solution for coating slow-release drug, cleaning with ultrapure water for 3 times (each time for 3 min) after soaking for 2h, and drying with nitrogen to obtain amnion or micro-droplet drug-loaded composite dressing.
Example twenty-five
The amnion/micro-droplet drug-loaded composite dressing is realized by spraying water micro-droplets on the inner surface of the amnion, and the amnion is artificially synthesized and comprises the following steps:
step 2501 preparation of first aqueous micro-droplets: adding dextran, trehalose and gelatin solutions with mass percentage concentrations of 1.5 wt%, 0.5 wt% and 0.5 wt% into a polyethylene glycol solution with mass percentage concentration of 6.5 wt% to form a fibril network, adding 1 wt% of egg white lysozyme, and reacting for 10 hours at the temperature of 60 ℃ and the rotation speed of 100rpm to form first water micro-droplets with the diameter of 5 nm;
step 2502 preparation of aqueous microdroplets of encapsulated drugs: dissolving 25mg of water micro-droplets and the sustained-release drug in 10ml of aqueous solution according to the mass ratio of 25:1, and reacting for 5 hours at the temperature of 4 ℃ and the rotation speed of 250rpm to obtain the water micro-droplets wrapping the drug;
step 2503, obtaining the amnion, namely soaking the placenta, which is produced by healthy lying-in women in a cesarean section, in an amnion preservation solution containing penicillin, streptomycin, penicillin and normal saline for 30min, washing for a plurality of times until the bloodstains on the placenta are washed, then performing blunt separation on the amnion from the chorion of the placenta, flatly paving the upper surface of the classified amnion on surgical adhesive paper, and soaking the surgical adhesive paper adhered with the amnion in the normal saline containing antibiotics for 30min to obtain the amnion, wherein the size of the amnion is 2cm × 4cm slices;
step 2504, adhering the micro-droplets of water and water wrapped with the medicine on the inner surface of the amnion: spraying the solution containing the water micro-droplets for wrapping the slow-release medicament on the inner surface of the amnion by using a spraying instrument, and then drying by using nitrogen to obtain the amnion or the composite dressing of the micro-droplets for wrapping the medicament.
TABLE II anti-inflammatory drug concentration
Example twenty-six
Test for reducing scars of compound dressing with medicament encapsulated in amnion or micro-droplet
The mouse (weight is about 500 g) is used in the experiment, two wounds with the area of 2cm × 2cm are burned by strong acid at the belly of the mouse, and the two wounds are respectively covered by common dressings and the amnion or micro-droplet drug-loaded composite dressings prepared in the twenty-two to twenty-five embodiments, the vernier caliper is used for detecting the area of scars after 5 days, 10 days, 20 days, 30 days, 40 days, 50 days and 60 days of wound healing, and fig. 3 is a schematic view of wound healing and scar reduction for treating the chronic ulcer mouse provided by the embodiment of the utility model, and is shown in fig. 3.
Example twenty-seven
In vitro cell experiment for testing cytotoxicity of amnion/micro-droplet composite dressing
Taking mouse fibroblast cells in logarithmic growth phase, inoculating the mouse fibroblast cells into a 96-well culture plate, and inoculating the mouse fibroblast cells into each well
1.5/m L× 104/m L cell suspension 200 mu L is cultured for 24 hours, and a cytotoxicity test is carried out by adopting an MTT cell proliferation and cytotoxicity detection kit, wherein the test is divided into an experimental group, a negative control group and a positive control group, the experimental group comprises four groups of composite dressings which are respectively prepared by twenty-two to twenty-five examples and contain amnion or micro-droplet medicaments, the negative control group comprises cell culture solution, the positive control group comprises common dressings, the experimental group, the negative control group and the positive control group are operated according to the steps of the kit, finally, the absorbance at 570nm is measured by using a microplate reader, the relative cell proliferation percentage (RGR) is calculated, the cytotoxicity grade is evaluated, the result is shown in the third table, the cytotoxicity of the experimental group is obviously lower than that of the positive control group, and the safety performance is obviously improved.
TABLE III comparison of measurement results
To sum up, the embodiment of the present invention provides a method for preparing a composite dressing with an amnion or micro-droplet encapsulated drug, the method comprises preparing first micro-droplets of water and respectively, preparing micro-droplets of water and respectively encapsulating a slow-release drug, preparing an amnion, and adhering the micro-droplets of water and respectively encapsulating the drug to the inner surface of the amnion, wherein the amnion is derived from the placenta of a senior animal, and the amnion is obtained under aseptic operation; furthermore, the water micro-droplets wrapping the slow-release drugs are uniformly adhered to the inner surface of the amnion, in the method, the water micro-droplets wrapping the slow-release drugs adhered to the inner surface of the amnion can be used as a carrier of the slow-release drugs and an adhesive, and have no biocompatibility and toxicity, so that the safety is improved, and the drug-loading capacity is increased; the dressing solves the problems that the dressing in the prior art does not have self-adhesion, and the cost is relatively high due to the fact that the dressing needs to be assisted for fixing.
While the preferred embodiments of the present invention have been described, additional variations and modifications in those embodiments may occur to those skilled in the art once they learn of the basic inventive concepts. It is therefore intended that the appended claims be interpreted as including the preferred embodiment and all such alterations and modifications as fall within the scope of the invention.
It will be apparent to those skilled in the art that various changes and modifications may be made without departing from the spirit and scope of the invention. Thus, if such modifications and variations of the present invention fall within the scope of the claims and their equivalents, the present invention is also intended to include such modifications and variations.
Claims (6)
1. An amnion or microdroplet drug-loaded composite dressing, comprising: dressing, amnion, and water micro-droplet coated with slow-release medicine;
the aqueous micro-droplets wrapping the slow-release drugs are adhered to the inner surface of the amnion;
the amnion is adhered to the inner surface of the dressing through the water micro-droplets wrapping the slow-release drug.
2. The composite dressing of claim 1, wherein said aqueous microdroplets encapsulating the slow-release drug have a diameter of 3nm to 7 nm.
3. The composite dressing of claim 1, wherein said aqueous microdroplets encapsulating the slow-release drug have a diameter of 5 nm.
4. The composite dressing of claim 1, wherein said amniotic membrane is sized according to the area of use.
5. The composite dressing of claim 1, wherein said slow release drug is: anti-inflammatory drugs, or antibacterial drugs, or wound healing drugs.
6. The composite dressing of claim 1, wherein said amniotic membrane comprises the placenta of a parturient, porcine, bovine, ovine mammal;
and when the puerpera, the pig, the cattle and the sheep are detected before delivery, the placenta donor hepatitis B surface antigen, the AIDS antigen, the chlamydia, the syphilis and the cytomegalovirus are negative.
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