KR101277509B1 - Tissue Adhesion prevention film including Polyoctylcyanoacrylate and Manufacturing Method thereof - Google Patents

Abstract

The present invention relates to a tissue adhesion preventing film containing polyoctylcyanoacrylate and a method for manufacturing the same, which is biodegradable in the human body, and includes an antibiotic or an anti-inflammatory agent, so that the tissue adhesion preventing film is decomposed in the human body. It is intended to help the treatment of the human body by having the characteristics of sustained-release drugs that release antibiotics or anti-inflammatory drugs slowly. According to the present invention, polyoctylcyanoacrylate is added and dissolved in an organic solvent to prepare a polyoctylcyanoacrylate mixture, and then antibiotics or anti-inflammatory agents are added to the polyoctylcyanoacrylate mixture and stirred to prevent tissue adhesion. It comprises the steps of preparing the stock solution, the raw material for preventing tissue adhesion to the mold, followed by drying at room temperature for 3 to 5 hours to prepare a film for preventing tissue adhesion, and drying the drying film for preventing tissue adhesion in the dryer Provided are a tissue adhesion preventing film and a manufacturing method thereof.

Description

Tissue Adhesion prevention film including Polyoctylcyanoacrylate and Manufacturing Method, including polyoctylcyanoacrylate

The present invention relates to a tissue adhesion preventing film and a method of manufacturing the same, and more specifically, biodegradable in the human body, and includes an antibiotic or anti-inflammatory agent, so that the antibiotic or anti-inflammatory agent gradually breaks down as the tissue adhesion prevention film is decomposed in the human body. The present invention relates to a film for preventing tissue adhesion including biodegradable polyoctylcyanoacrylate (Poly Octylcyanoacrylate) having the properties of a sustained-release preparation to be useful for the treatment of the human body and a method of manufacturing the same.

Tissue adhesion refers to the combination of abnormal fibrous connective tissue with other tissues that may occur during natural healing of wounds formed in the abdominal cavity after surgical open surgery. This is a natural phenomenon, but if the site where the tissue adhesion occurs is not appropriate, it may cause pain or discomfort to the patient or cause dysfunction, and may require reoperation to remove the adhesion. It is a problem in the fields of vascular surgery, gastrointestinal surgery and obstetrics and gynecology, which may threaten the patient's life, thus causing tissue adhesion or delaying adhesion.

For this reason, a thin membrane film type or gel type tissue adhesion prevention film is used to prevent adhesion of skin or organ tissues to the surgical site. The membrane film type is easily bendable to fit anatomical structures and does not allow tissue interaction. Because it is easy to form a barrier film, it is used for large areas of surgery such as laparotomy and reconstruction of skin or organ tissue over a long period of time. Gel-type adhesion barrier is narrow for 1 to 2 weeks, like abdominal surgery. Apply to the area where tissue is rebuilt. In addition, a variety of methods are used to prevent tissue adhesion. There are methods of minimizing the adhesion of the surface of the intestinal membrane through intraperitoneal washing or adding heparin solution.

However, in the case of the membrane film type, the film may adhere to skin or organ tissues, and the film may be contaminated with bacteria. In addition, the method of using a gel-type anti-adhesion film, intraperitoneal washing, and heparin solution has a problem in that it is applied to a surgical technique and has limitations in application area.

Accordingly, an object of the present invention is to provide a tissue adhesion preventing film and a method for manufacturing the same, including polyoctylcyanoacrylate, which is a material that is biodegradable in the human body without adhesion to skin or organ tissues.

Another object of the present invention is to provide an anti-tissue adhesion film and a method for manufacturing the same, wherein antibiotics or anti-inflammatory agents present therein are gradually released while the anti-tissue adhesion film is biodegraded, thereby suppressing bacterial growth and helping the wound recovery of the human body.

The present invention for achieving the object as described above provides a film for preventing tissue adhesion comprising polyoctylcyanoacrylate and antibiotics or anti-inflammatory agents.

Here, the molecular weight of the polyoctylcyanoacrylate may be 100,000 to 300,000.

And the antibiotics are gramicidine, nalidixic acid, neomycin, nonnectin, norfloxacin, bacitracin, cephalosporin, streptomycin, aminoglycosides, actonomycin, ampicillin, kanamycin, quinolone, chloramphenicol, At least one selected from the group consisting of teramicin, tetracycline, patulin and penicillin, wherein the anti-inflammatory agent is glucamethasine, nabumethone, naproxen, nimesuride, dexamethasone, dexibuprofen, diclofenac, diflunisal, Ronazolac, Ronoxicam, Roxoprofen, Mecrofenamic Acid, Mefenamic Acid, Meloxycamp, Moniflumate, Benolate, Bromelain, Salicylic Acid Imidazole, Cerathiopeptidase, Celecoxib, Sulfonate Lindac, Synoxycam, Acemetasin, Aceclofenac, Aspirin, Alminopropene, Amfenac Sodium, Emorphazone, Etodolac, Benzidamine Hydrochloride, Propacetamol Hydrochloride, Oxapro , Ibuprofen, ibuproxam, indomethacin, zaltoprofen, ketorolac, ketoprofen, clonicin, talniflumate, tenoxycam, tolmethine sodium, tolphenic acid, thiapropenic acid, phenopropene, penti One or more selected from the group consisting of azac, pelubiprofen, pranopropene, proglumetacin, progestogens, flurbiprofen, flufenamic acid, pyrazinobutazone, and pyroxicam.

Meanwhile, the present invention prepares a polyoctylcyanoacrylate mixture by adding and dissolving polyoctylcyanoacrylate to an organic solvent, and then adds and stirs an antibiotic or an anti-inflammatory agent to the polyoctylcyanoacrylate mixture to prevent tissue adhesion. Preparing a stock solution, adding the stock solution for preventing tissue adhesion to a mold, and drying the film for 3 to 5 hours at room temperature to prepare a film for preventing tissue adhesion, and a drying step of drying the film for preventing tissue adhesion in a dryer. It provides a method for producing a tissue adhesion prevention film characterized in that.

Here, the preparing of the tissue adhesion preventing stock solution may be performed by adding and dissolving 1 to 20 parts by weight of the polyoctylcyanoacrylate based on 100 parts by weight of the organic solvent to prepare the polyoctylcyanoacrylate mixture. The anti-tissue cyanoacrylate mixture may be prepared by adding and stirring 0.001 to 0.5 parts by weight of the antibiotic or anti-inflammatory agent based on 100 parts by weight of the organic solvent.

In addition, the organic solvent is ethyl acetate, methylene chloride, benzene, chloroform, methyl alcohol, ethyl alcohol, acetone, alkaline water, toluene, xylene, dimethyl formamide, dimethyl sulfoxide, trifluoro acetic acid, trifluoro ethylene, One or more from the group consisting of hexa fluoro isopropanol, methylene chloride and tetra hydrofuran.

And also, the drying step may be to dry for 3 to 5 hours in a 50 to 70 ℃ state.

The film for preventing tissue adhesion according to the present invention is formed to a thickness of 50 to 200㎛ does not occur adhesion to the skin or organ tissues, and contains polyoctylcyanoacrylate, which can be biodegradable in the human body.

In addition, the anti-tissue adhesion film according to the present invention includes an antibiotic or anti-inflammatory agent therein, while having the characteristics of the sustained-release formulation in which the antibiotic or anti-inflammatory agent was released slowly as the tissue adhesion prevention film is degraded, inhibiting bacterial growth It can have the effect of blocking inflammation.

Figure 1 is a schematic diagram showing the manufacturing process of the polyoctylcyanoacrylate used in the present invention.
Figure 2 is a flow chart showing a method for producing a tissue adhesion preventing film containing polyoctylcyanoacrylate according to the present invention.

In the following description, only parts necessary for understanding the operation according to the embodiment of the present invention will be described, it should be noted that the description of other parts will be omitted so as not to obscure the subject matter of the present invention.

Also, the terms and words used in the present specification and claims should not be construed to be limited to ordinary or dictionary meanings, and the inventor is not limited to the concept of terms in order to describe his invention in the best way. It should be construed in accordance with the meaning and concept consistent with the technical idea of the present invention based on the principle that it can be properly defined. Therefore, the embodiments described in the present specification and the configurations shown in the drawings are merely one preferred embodiment of the present invention, and not all of the technical ideas of the present invention are described. Therefore, It is to be understood that equivalents and modifications are possible.

The present invention improves biodegradability using polyoctylcyanoacrylate produced as a by-product when producing octylcyanoacrylate, and includes polyoctylcyanoacrylate which helps to recover the wound by adding antibiotics or anti-inflammatory agents. It relates to a tissue adhesion preventing film and a method for producing the same.

Polyoctylcyanoacrylates used in the present invention are by-products produced in the process of producing octylcyanoacrylates, and all of them have been discarded.

The manufacturing process of the polyoctyl cyanoacrylate used by this invention is shown in FIG.

Looking at this in detail, the step of reacting cyanoacetic acid (cyannoacetic acid) and octane alcohol in a 1: 1 equivalent ratio in the presence of a solvent to prepare octylcyanoacetate; Reacting the octylcyanoacetate and paraformaldehyde in a 1: 1 equivalent ratio in the presence of a solvent; When the reaction is completed, after removing the solvent to separate and purify octylcyanoacrylate; And purifying octylcyanoacrylate and obtaining polyoctylcyanoacrylate from the remaining by-products.

At this time, the solvent used in each reaction process may include an organic solvent commonly used in the art, for example, benzene, toluene or xylene may be used, but is not limited thereto.

In addition, the polyoctylcyanoacrylate can be obtained by purifying by-products with silica gel, the content of which is preferably 0.001 to 4% by weight based on the total weight of the composition.

In the present invention, a polyoctylcyanoacrylate having a molecular weight of 100,000 to 300,000 may be used, but is not limited thereto.

However, when the polyoctylcyanoacrylate having a molecular weight of less than 100,000 is used, the tensile strength of the film to be produced is weak, which may be easily broken by external force. If the molecular weight exceeds 300,000, the tensile strength may be improved, but it may be absorbed in vivo. There is a problem that the length of time that can be long.

Antibiotics used in the present invention are gramicidine, nalidixic acid, neomycin, nonactin, norfloxacin, vacitracin, cephalosporin, streptomycin, aminoglycosides, actonomycin, ampicillin, kanamycin, quinolone, It may be at least one selected from the group consisting of chloramphenicol, teramycin, tetracycline, patulin and penicillin, and the anti-inflammatory agent used in the present invention is glucamethasine, nabumethone, naproxen, nimesuride, dexamethasone, dexibuprofen, diclofenac , Diflunisal, Ronazolac, Ronoxicam, Roxopropene, Mecrofenamic Acid, Mefenamic Acid, Meloxycam, Moniflumate, Benorylate, Bromelain, Salicylic Acid Imidazole, Cerathiopeptidase, Celecoxib, sulindac, synoxycam, acemethacin, aceclofenac, aspirin, aminopropene, ampfenac sodium, emolfazone, etodolak, benzidamine hydrochloride, hydrochloric acid Propacetamol, oxaprozin, ibuprofen, ibuproxam, indomethacin, zaltoprofen, ketorolac, ketoprofen, clonicin, talniflumate, tenoxycam, tolmethinate sodium, tolpenomic acid, thiapro From the group consisting of phenic acid, phenopropene, pentiazac, pelubiprofen, pranopropene, proglumetacin, progestogens, flurbiprofen, flufenamic acid, pyrazinobutazone and pyroxicam One or more may be selected, but is not limited thereto.

Figure 2 is a flow chart according to the method for producing a tissue adhesion preventing film containing polyoctylcyanoacrylate according to an embodiment of the present invention.

In step S10 to prepare a stock solution for preventing tissue adhesion. More specifically, polyoctylcyanoacrylate is added to and dissolved in an organic solvent to prepare a polyoctylcyanoacrylate mixture, followed by addition and stirring of an antibiotic or an anti-inflammatory agent to the polyoctylcyanoacrylate mixture. Prepare a preventive stock solution.

The organic solvent used here is ethyl acetate, methylene chloride, benzene, benzene, chloroform, methyl alcohol, ethyl alcohol, acetone, alkaline water. (Alkaline Water), Toluene, Xylene, Dimethyl Formamide, Dimethyl Sulfoxide, Trifluoro Acetic Acid (TFA), Trifluoro Ethylene (TFE) One or two mixed solvents selected from the group consisting of Trifluoro Ethylene, Hexa Fluoro isopropanol (HFIP), Methylene chloride (MC), Tetra Hydro Furan (THF) But it is not limited thereto.

Here, the preparing of the tissue adhesion preventing stock solution may be performed by adding and dissolving 1 to 20 parts by weight of polyoctylcyanoacrylate based on 100 parts by weight of an organic solvent to prepare a polyoctylcyanoacrylate mixture. It may be to prepare a stock solution for preventing tissue adhesion by adding and stirring 0.001 to 0.5 parts by weight of antibiotics or anti-inflammatory agents based on 100 parts by weight of the organic solvent to the rate mixture.

When preparing a polyoctylcyanoacrylate mixture in the step of preparing a tissue adhesion preventing stock solution, if the mixing ratio of polyoctylcyanoacrylate exceeds 20 parts by weight based on 100 parts by weight of an organic solvent, polyoctylcyano When the viscosity of the acrylate mixture is greater than the appropriate value, it becomes difficult to prepare a uniform mixture, making it difficult to produce a film having a thickness of 200 μm or less, and when the mixing ratio of polyoctylcyanoacrylate is less than 1 part by weight, The viscosity of the octylcyanoacrylate mixture may be less than an appropriate value such that the thickness of the film is less than 50 μm, resulting in a drop in commodity value.

Subsequently, a film for preventing tissue adhesion is prepared in step S20. More specifically, the tissue adhesion prevention stock solution is added to a mold, followed by drying at room temperature for 3 to 5 hours to prepare a tissue adhesion prevention film.

Here, the room temperature means about 15 to 25 ℃, in the step of preparing a film for preventing tissue adhesion, if the heat is applied above room temperature may cause wrinkles in the film for preventing tissue adhesion, there is a fear that the product value.

Subsequently, in step S30, the tissue adhesion prevention film may be dried in a dryer to prepare a finished product of the tissue adhesion prevention film.

Wherein the drying step may be to dry for 3 to 5 hours at a temperature of 50 to 70 ℃, by this step can effectively remove the organic solvent contained in the film for preventing tissue adhesion.

On the other hand, while the anti-tissue adhesion film produced during the drying step, the antibiotic or anti-inflammatory agent may be dried to include an antibiotic or anti-inflammatory agent in an amount less than the appropriate amount, the antibiotic or anti-inflammatory agent to the tissue adhesion prevention film produced by the above-described manufacturing process It may further comprise the step of applying.

Claims (9)

delete delete delete After adding and dissolving polyoctylcyanoacrylate in an organic solvent to prepare a polyoctylcyanoacrylate mixture, an antibiotic or anti-inflammatory agent is added to the polyoctylcyanoacrylate mixture and stirred to prepare a stock solution for preventing tissue adhesion. step;
Preparing the film for preventing tissue adhesion by injecting the tissue adhesion preventing stock solution into a mold and drying at room temperature for 3 to 5 hours; And
Drying step of drying the tissue adhesion prevention film in a dryer;
An application step of applying the antibiotic or anti-inflammatory agent to the dried tissue adhesion prevention film; Lt; / RTI >
Preparing the stock solution for preventing tissue adhesion,
After adding and dissolving 1 to 20 parts by weight of the polyoctylcyanoacrylate based on 100 parts by weight of the organic solvent to prepare the polyoctylcyanoacrylate mixture,
To prepare a solution for preventing tissue adhesion by adding and stirring 0.001 to 0.5 parts by weight of the antibiotic or anti-inflammatory agent based on 100 parts by weight of the organic solvent to the polyoctylcyanoacrylate mixture,
The drying step,
Method for producing a tissue adhesion prevention film characterized in that the drying for 3 to 5 hours at 50 to 70 ℃ state. delete 5. The method of claim 4,
The molecular weight of the polyoctylcyanoacrylate is a method for producing a tissue adhesion preventing film, characterized in that 100,000 to 300,000. The method of claim 4, wherein the antibiotic is
Gramicidine, nalidixic acid, neomycin, nonactin, norfloxacin, bacitracin, cephalosporin, streptomycin, aminoglycoside, actotomycin, ampicillin, kanamycin, quinolone, chloramphenicol, teramycin, tetracycline, At least one selected from the group consisting of patulin and penicillin,
The anti-inflammatory agent,
Glucametacin, Nabumeton, Naproxen, Nimesuride, Dexamethasone, Dexibuprofen, Diclofenac, Diflunisal, Ronazolac, Ronoxicam, Roxoprofen, Mecrofenamic acid, Mefenamic acid, Meloxycham, Monika Flumate, benolylate, bromelain, salicylic acid imidazole, ceratipeptidase, celecoxib, sulindac, synoxycam, acemethacin, aceclofenac, aspirin, aminopropene, ampenac sodium, emol Fazon, etodolac, benzidamine hydrochloride, propacetamol hydrochloride, oxaprozin, ibuprofen, ibuprosam, indomethacin, zaltoprofen, ketorolac, ketoprofen, clonicin, talniflumate, tenoxycam Sodium tolmetin, tolphenamic acid, thiapropenic acid, phenopropene, pentiazac, pelubiprofen, pranopropene, proglumetacin, progestogens, flurbiprofen, flufenamic acid, pyrazi From the group consisting of nobutazone and pyroxicam Or above method of producing a tissue adhesion prevention film, characterized in that selected. The method of claim 4, wherein the organic solvent,
Ethyl acetate, methylene chloride, benzene, chloroform, methyl alcohol, ethyl alcohol, acetone, alkaline water, toluene, xylene, dimethyl formamide, dimethyl sulfoxide, trifluoro acetic acid, trifluoro ethylene, hexafluoro isopropanol, methylene chloride And tetrahydrofuran method for producing a tissue adhesion preventing film, characterized in that at least one selected from the group consisting of. delete

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