CN112870180B - Diclofenac sodium abdominal navel patch suitable for postoperative pain relief of anorectal and preparation method thereof - Google Patents
Diclofenac sodium abdominal navel patch suitable for postoperative pain relief of anorectal and preparation method thereof Download PDFInfo
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- 229960001193 diclofenac sodium Drugs 0.000 title claims abstract description 93
- JGMJQSFLQWGYMQ-UHFFFAOYSA-M sodium;2,6-dichloro-n-phenylaniline;acetate Chemical compound [Na+].CC([O-])=O.ClC1=CC=CC(Cl)=C1NC1=CC=CC=C1 JGMJQSFLQWGYMQ-UHFFFAOYSA-M 0.000 title claims abstract description 93
- 238000002360 preparation method Methods 0.000 title claims abstract description 18
- 208000004550 Postoperative Pain Diseases 0.000 title claims abstract description 10
- 230000003187 abdominal effect Effects 0.000 title abstract description 18
- 239000003814 drug Substances 0.000 claims abstract description 92
- 239000001856 Ethyl cellulose Substances 0.000 claims abstract description 68
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims abstract description 68
- 229920001249 ethyl cellulose Polymers 0.000 claims abstract description 68
- 235000019325 ethyl cellulose Nutrition 0.000 claims abstract description 68
- 229940079593 drug Drugs 0.000 claims abstract description 28
- 210000001015 abdomen Anatomy 0.000 claims abstract description 22
- 230000001681 protective effect Effects 0.000 claims abstract description 20
- 239000004820 Pressure-sensitive adhesive Substances 0.000 claims abstract description 10
- 230000002980 postoperative effect Effects 0.000 claims abstract description 8
- 239000012528 membrane Substances 0.000 claims abstract description 7
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 239000000243 solution Substances 0.000 claims description 18
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- 238000000034 method Methods 0.000 claims description 13
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- RZVAJINKPMORJF-UHFFFAOYSA-N Acetaminophen Chemical compound CC(=O)NC1=CC=C(O)C=C1 RZVAJINKPMORJF-UHFFFAOYSA-N 0.000 description 6
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 6
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- 230000001070 adhesive effect Effects 0.000 description 3
- 229960002428 fentanyl Drugs 0.000 description 3
- PJMPHNIQZUBGLI-UHFFFAOYSA-N fentanyl Chemical compound C=1C=CC=CC=1N(C(=O)CC)C(CC1)CCN1CCC1=CC=CC=C1 PJMPHNIQZUBGLI-UHFFFAOYSA-N 0.000 description 3
- 238000001990 intravenous administration Methods 0.000 description 3
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- KPHWPUGNDIVLNH-UHFFFAOYSA-M diclofenac sodium Chemical compound [Na+].[O-]C(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl KPHWPUGNDIVLNH-UHFFFAOYSA-M 0.000 description 2
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- 206010000059 abdominal discomfort Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
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- 230000003110 anti-inflammatory effect Effects 0.000 description 1
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Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
- A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/196—Carboxylic acids, e.g. valproic acid having an amino group the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0014—Skin, i.e. galenical aspects of topical compositions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The invention discloses a diclofenac sodium abdominal navel patch suitable for postoperative pain relief of anorectal, and belongs to the technical field of medicines. The diclofenac sodium navel plaster comprises a backing layer, a navel plaster body and a protective film, wherein the navel plaster body is covered on the backing layer, and the protective film is covered on the surface of the navel plaster body; the abdomen navel plaster body is formed by a quick-release medicine area, a quick-release medicine area and a pasting area from the center of a circle outwards in sequence, wherein the quick-release medicine area comprises a diclofenac sodium gel layer and a medical elastic sponge coated with a non-porous ethyl cellulose membrane, the quick-release medicine area comprises a porous ethyl cellulose membrane layer and a diclofenac sodium gel layer, and the pasting area is a pressure-sensitive adhesive. The abdomen navel patch provided by the invention not only overcomes the defects of slow effect, large gastrointestinal side effect and the like of the diclofenac sodium oral preparation, but also avoids severe pain caused by stimulation to an anorectal postoperative wound when the suppository is inserted, has the advantages of quick effect, long pain relieving time, convenience in use and the like, and is particularly suitable for pain relieving after anorectal operation.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to a diclofenac sodium abdominal navel patch suitable for postoperative pain relief of anorectal and a preparation method thereof.
Background
The operation is the most effective treatment means for anal fistula, anal fissure, mixed hemorrhoids and other anorectal diseases, the physiological function and anatomical characteristics of the anus determine that the operation wound surface can only be opened, the nerve endings in the anus area are densely distributed, and the defecation, the anorectal peristalsis, the cleaning and dressing change and the like can cause severe pain, so that a plurality of complications such as difficult defecation and urinary retention are caused, and the postoperative rehabilitation and the life quality of patients are seriously affected, so that safe, effective, economic and suitable analgesic drugs, dosage forms and administration routes are particularly important for anorectal operation patients.
At present, oral non-steroidal analgesics or intravenous drip fentanyl, morphine and other opioid analgesics are commonly adopted for the postoperative pain relief of anorectal, but the oral non-steroidal analgesics have the defects of strong gastrointestinal tract irritation, large first pass effect (low bioavailability), slow onset of action, unsatisfactory pain relief effect and the like, and have great harm to the physical health of patients, while the intravenous drip fentanyl and morphine analgesics have adverse reactions such as nausea and vomiting, urinary retention, skin itch, respiratory depression and the like.
Sodium diclofenac is a novel powerful anti-inflammatory analgesic, is a powerful inhibitor of prostaglandin synthetase, and reduces synthesis and release of prostaglandin in vivo by inhibiting the action of prostaglandin synthetase, so that pain can be relieved and eliminated. The diclofenac sodium suppository has remarkable analgesic effect, convenient administration and less adverse reaction, and is widely used for postoperative analgesia such as caesarean section, lumbar vertebra operation, benign prostatic hyperplasia excision and the like, but the diclofenac sodium suppository used for anorectal operation can cause severe pain and sense of weight when the diclofenac sodium suppository is plugged into anus, thereby increasing the pain of patients and being not easy to be accepted by the patients.
Therefore, the clinical urgent need is that the diclofenac sodium preparation which can be fast and effective, has long duration of action, low side effect, convenient use and little pain is developed and used for the postoperative analgesia of anorectal operation.
Disclosure of Invention
Aiming at the defect of lack of ideal analgesic measures or medicines after anorectal operation, the invention provides the diclofenac sodium abdominal navel patch suitable for anorectal operation, which has the advantages of quick and durable effect, convenient use and the like, is particularly suitable for anorectal operation, can overcome the defects of strong gastrointestinal tract irritation, low bioavailability, excessively slow effect, short analgesic effect and the like of oral non-steroidal analgesic, can also avoid adverse reactions such as nausea and vomiting, urinary retention, skin itch, respiratory depression and the like of intravenous drip fentanyl and morphine analgesic, and solves the severe pain caused by wound irritation after anorectal operation when the diclofenac sodium suppository is plugged, thereby having better clinical application value and significance.
In order to achieve the above object, the present invention adopts the following technical scheme:
the diclofenac sodium navel patch suitable for the postoperative pain relief of anorectal comprises a backing layer, a navel patch body and a protective film, wherein the navel patch body is covered on the backing layer, and the protective film is covered on the surface of the navel patch body;
the abdomen navel patch body is sequentially provided with a quick medicine releasing area, a medicine controlling and releasing area and a pasting area from the center of the circle outwards;
the quick-release medicine region comprises a diclofenac sodium gel layer and a medical elastic sponge coated with a nonporous ethyl cellulose membrane, the diclofenac sodium gel layer is coated on the medical elastic sponge coated with the nonporous ethyl cellulose membrane, and the surface of the medical elastic sponge coated with the nonporous ethyl cellulose membrane is adhered on the backing layer;
the quick-release medicine control region comprises a porous ethyl cellulose film layer and a diclofenac sodium gel layer, wherein the porous ethyl cellulose film layer covers the surface of the diclofenac sodium gel layer, and the diclofenac sodium gel layer is coated on the back lining layer;
the pasting area is pressure sensitive adhesive.
Further, the area ratio of the quick release medicine region to the controlled release medicine region is 2:3.
further, the medical elastic sponge is in a hemispheroidal shape.
Further, the nonporous ethylcellulose film is made from an ethanol solution of 20wt.% ethylcellulose.
Further, the diclofenac sodium gel layer is prepared from the following raw materials in percentage by weight: 0.5-2% of diclofenac sodium, 0.5-1.2% of carbomer, 6-20% of propylene glycol, 0.4-1.5% of triethanolamine and the balance of distilled water; the sum of the weight percentages of all the raw materials is 100 percent.
Further, the porous ethyl cellulose membrane layer is made of an ethanol solution of ethyl cellulose and polyethylene glycol 400, the total mass concentration of the ethyl cellulose and the polyethylene glycol 400 is 50%, and the weight ratio of the ethyl cellulose to the polyethylene glycol 400 is 9:1.
The preparation method of the diclofenac sodium abdominal navel patch comprises the following steps:
step 1, cutting a medical elastic sponge into a hemispherical shape matched with the navel of a human body, placing the hemispherical shape in an ethanol solution of 20wt.% ethyl cellulose, taking out the hemispherical shape, drying the hemispherical shape to obtain the medical elastic sponge coated with a nonporous ethyl cellulose film, and then bonding the medical elastic sponge on a backing layer;
step 2, dissolving diclofenac sodium in a mixed solution of propylene glycol and distilled water, boiling, cooling to 50-70 ℃, adding carbomer, adding triethanolamine after swelling to obtain diclofenac sodium gel, and coating the diclofenac sodium gel on the surface of a medical elastic sponge coated with a nonporous ethylcellulose film in a quick-release medicine area and the surface of a backing layer in a quick-release medicine area to form a diclofenac sodium gel layer;
step 3, mixing ethyl cellulose and polyethylene glycol 400, dissolving in 95% ethanol solution, pouring the mixed solution into a mold, drying to obtain a porous ethyl cellulose film, and covering the porous ethyl cellulose film on a diclofenac sodium gel layer in a drug release control region to form a porous ethyl cellulose film layer;
step 4, coating a pressure-sensitive adhesive on the backing layer to form a sticking area;
and 5, covering the protective film on the abdomen-navel paste body to obtain the diclofenac sodium abdomen-navel paste.
Further, the thickness of the diclofenac sodium gel layer is 2-6mm.
Further, the thickness of the porous ethylcellulose film layer is 2mm.
Compared with the prior art, the invention has the beneficial effects that:
1. the diclofenac sodium is prepared into the navel patch (a brand new percutaneous absorption preparation which is designed by self) for the first time, and the navel patch body is respectively provided with a quick medicine releasing area, a medicine releasing control area and a pasting area from inside to outside, which is different from the simple navel patch. The diclofenac sodium abdominal plaster has rapid and durable analgesic effect, avoids adverse reactions such as nausea, vomit, diarrhea, upper abdominal pain, stomach discomfort, gastric ulcer, gastric mucosa hemorrhage, dyspepsia, acid regurgitation and the like caused by oral administration of diclofenac sodium, solves the problem of severe pain caused by stimulation to an anorectal postoperative wound when the diclofenac sodium suppository is inserted, and is particularly suitable for anorectal postoperative pain relieving.
2. The navel of a human body is concave, and medicines in the common navel patch sold at present are difficult to be in close contact with the skin in the navel, so that the medicine absorption is affected. According to the shape and structure characteristics of human navel and belly skin, the medical elastic sponge hemispheroids which can be matched with the human navel and are wrapped by the nonporous ethyl cellulose films are adhered to the middle position of the navel-attached body, the elastic effect of the medical elastic sponge hemispheroids is skillfully utilized to enable the diclofenac sodium gel to be tightly filled on the whole navel inner skin, the nonporous ethyl cellulose films prevent the diclofenac sodium from penetrating into the medical elastic sponge hemispheroids, and the navel (called Shenque acupoint in traditional Chinese medicine) skin is thinner and has rich blood vessel distribution, so that the medical elastic sponge hemispheroids are particularly beneficial to rapid absorption of medicines, a rapid medicine releasing area is formed, and the effect of rapid postoperative pain relieving of anus and intestines is achieved.
3. The quick-release medicine area around the quick-release medicine area is composed of diclofenac sodium gel coated on a back lining layer and a porous ethyl cellulose film covered on the gel, and the medicine slowly and uniformly permeates through medicine release pores on the ethyl cellulose film and is absorbed through the abdominal skin around the navel to maintain the long-time postoperative analgesic effect of anorectum. When the ethyl cellulose film containing the pore-forming agent is covered on the hydrogel, the water provided by the hydrogel can dissolve the pore-forming agent to generate small drug release holes, so that the drug release rate can be controlled by adjusting the addition amount of the pore-forming agent, and the sustained drug release time is regulated and controlled within a preset range. Experimental results show that when the ratio of the ethylcellulose to the pore-forming agent polyethylene glycol 400 is 90:10, the sustained release time of the prepared diclofenac sodium abdominal navel patch can reach about 24 hours, namely the analgesic maintenance time after anorectal operation can reach 24 hours.
4. The abdomen navel patch can meet the requirement of quick acting of the medicine and can reach the dosage required by the expected effective duration by adjusting the thickness of gel coated on the quick-release medicine area and the quick-release medicine area, the medicine concentration and the area of the quick-release medicine area.
The diclofenac sodium navel patch provided by the invention has the advantages that the effect is rapid, the medicine is slowly and continuously released due to the addition of the medicine release control area, the continuous analgesic time reaches 24 hours through the absorption of the abdominal skin around the navel, the defects of slow effect, frequent medicine application and gastrointestinal adverse reaction of oral diclofenac sodium are overcome, the problem of severe pain caused by wound surface stimulation after anorectal operation when the diclofenac sodium suppository is inserted is solved, and the diclofenac sodium navel patch is particularly suitable for anorectal postoperative analgesic.
Drawings
FIG. 1 is a schematic cross-sectional view of a sodium diclofenac abdominal navel patch.
Fig. 2 is a schematic top view of the navel-applied body with the protective film removed.
Fig. 3 is a schematic bottom view of the abdominal umbilicus body with the backing layer removed.
Fig. 4 is a graph showing the cumulative release profile of diclofenac sodium navel patch in example 1.
Fig. 5 is a graph of the cumulative release profile of diclofenac sodium navel patch in example 2.
FIG. 6 is a graph showing the cumulative release profile of diclofenac sodium navel patch according to example 3.
In fig. 1 to 3, 1 is a protective film, 2.1 is a diclofenac sodium gel layer of a quick drug release region, 2.2 is a nonporous ethylcellulose film, 2.3 is a medical elastic sponge, 3.1 is a porous ethylcellulose film, 3.2 is a diclofenac sodium gel layer of a quick drug release region, 4 is a pressure sensitive adhesive, and 5 is a backing layer.
Detailed Description
As shown in fig. 1-3, the invention provides a diclofenac sodium navel patch suitable for postoperative pain relief of anorectal, which comprises a backing layer 5, a navel patch body and a protective film 1, wherein the navel patch body is covered on the backing layer, and the protective film is covered on the navel patch body surface.
The abdomen navel plaster body is sequentially provided with a quick medicine releasing area, a medicine controlling and releasing area and a pasting area from the center of the circle to the outside. The quick-release medicine region comprises a diclofenac sodium gel layer (2.1) and a medical elastic sponge (2.3) coated with a nonporous ethyl cellulose film (2.2), the diclofenac sodium gel layer (2.1) is coated on the surface of the medical elastic sponge coated with the nonporous ethyl cellulose film, and the medical elastic sponge coated with the nonporous ethyl cellulose film is bonded on a backing layer (5);
the quick-release medicine control region comprises a porous ethyl cellulose film layer (3.1) and a diclofenac sodium gel layer (3.2), wherein the porous ethyl cellulose film layer covers the surface of the diclofenac sodium gel layer, and the diclofenac sodium gel layer is coated on the back layer;
the pasting area is pressure sensitive adhesive (4).
The invention will now be described in further detail with reference to the drawings and specific examples, which should not be construed as limiting the invention. Modifications and substitutions to methods, procedures, or conditions of the present invention without departing from the spirit and nature of the invention are intended to be within the scope of the present invention. The experimental procedures and reagents not shown in the formulation of the examples were all in accordance with the conventional conditions in the art.
Example 1
1. Preparation of diclofenac sodium abdominal navel plaster
(1) Cutting medical elastic sponge into hemispherical shape capable of matching with human navel, placing into coating solution (20% ethyl cellulose ethanol solution) for 3min, taking out, drying at 42deg.C to obtain sponge hemisphere with surface coated with nonporous ethyl cellulose film, and bonding on the middle position of backing layer.
(2) The preparation method comprises the following steps of: 0.8% of diclofenac sodium, 0.8% of carbomer, 10% of propylene glycol, 0.8% of triethanolamine and the balance of distilled water, and the preparation steps are as follows: dissolving diclofenac sodium in a mixed solution of propylene glycol and distilled water, boiling, cooling to 55 ℃, scattering carbomer, swelling, adding triethanolamine, neutralizing, stirring to form gel, and uniformly coating on a medical elastic sponge hemisphere of a quick-release region and a backing layer of a quick-release region, wherein the thickness is 3mm, and the area ratio of the quick-release region to the quick-release region is 2:3.
(3) Mixing ethyl cellulose and water-soluble pore-forming agent polyethylene glycol 400 (the ratio is 9:1), dissolving in 95% ethanol solution (the total mass concentration of the ethyl cellulose and the polyethylene glycol 400 is 50%), pouring into a mould, drying at 42 ℃ to obtain a pore-forming agent-containing ethyl cellulose film with the thickness of 2mm, cutting, and covering the film on diclofenac sodium gel in a drug release control region.
(4) The medical pressure sensitive adhesive is coated on the backing layer of the adhesive area.
(5) Cutting the protective film (release paper) into a shape matched with the abdomen navel patch body and covering the abdomen navel patch body to obtain the diclofenac sodium abdomen navel patch which is particularly suitable for pain relief after anorectal operation.
2. In-vitro release degree determination test and result of diclofenac sodium abdominal navel patch
According to general rule of IV transdermal patch of second appendix of 2015 edition of Chinese pharmacopoeia, the drug release characteristics of the navel patch can be evaluated through an in vitro release degree measurement test, the specific method is carried out according to a fourth method (a method 2 device) of the four rule 0931 dissolution degree and release degree measurement method of 2015 edition of Chinese pharmacopoeia, 500ml of physiological saline is used as a release medium, the rotating speed is 50r & min < -1 >, the navel patch is taken, a protective film is removed, the protective film is placed between two layers of discs, the dissolution surface faces upwards, and the net disc is horizontally placed at the lower part of a dissolution cup, so that the net disc is parallel to the rotating surface of the bottom of a oar, and the distance between the net disc and the rotating surface is 25+/-2 mm. Taking 4ml of receiving solution at time points of 0h, 0.5h, 1h, 1.5h, 2h, 4h, 8h, 12h, 16h, 20h, 24h and 30h respectively, supplementing physiological saline with the same volume and temperature, measuring acetaminophen concentration by an ultraviolet spectrophotometer, measuring wavelength to 276nm, and calculating cumulative release degree according to the following formula: cumulative release (%) =t time the amount of drug released cumulatively/total amount of drug in the navel patch×100%.
The results of the in vitro release measurement test of diclofenac sodium navel patch are shown in table 1 and fig. 4.
Table 1: cumulative Release measurement result
| Sampling point numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
| Time (h) | 0 | 0.5 | 1 | 1.5 | 2 | 4 | 8 | 12 | 16 | 20 | 24 | 30 |
| Cumulative release (%) | 0 | 33.4 | 38.2 | 42.2 | 44.7 | 51.6 | 60.5 | 67.4 | 72.9 | 78.3 | 81.9 | 82.5 |
As is clear from the data and cumulative release profile in the table, the drug was released rapidly for the first 1 hour, the cumulative release reached 38.2% and then gradually slowed down to cumulative release of 44.7%, 51.6%, 60.5%, 67.4%, 72.9%, 78.3%, 81.9%, 82.5% for 2h, 4h, 8h, 12h, 16h, 20h, 24h, 30h, respectively, showing a uniform release profile. The ratio of the areas of the quick-release medicine area to the quick-release medicine area is 2:3, the thickness of the diclofenac sodium gel is the same (uniform coating), and the medicine contents of the quick-release medicine area and the quick-release medicine area are 40% and 60% respectively, so that the medicine in the quick-release medicine area can be considered to basically permeate completely within 1 hour to exert the quick-release analgesic effect, and then the medicine release speed in the quick-release medicine area is basically constant until the accumulated release degree of 24 hours reaches 81.9%, namely the analgesic effect can be maintained for 24 hours.
Example 2
1. Preparation of diclofenac sodium abdominal navel plaster
(1) Cutting medical elastic sponge into hemispheres which can be matched with human navel by using a die, placing the hemispheres into coating liquid (the coating liquid is 95% ethanol solution of ethyl cellulose) for 3min, taking out, drying at 45 ℃ to obtain medical elastic sponge hemispheres with surfaces coated with nonporous ethyl cellulose films, and bonding the medical elastic sponge hemispheres on the middle positions of backing layers.
(2) The preparation method comprises the following steps of: 1.2% of diclofenac sodium, 1.0% of carbomer, 12% of propylene glycol, 1.0% of triethanolamine and the balance of distilled water, and the preparation steps are as follows: dissolving diclofenac sodium in a mixed solution of propylene glycol and distilled water, boiling, cooling to 60 ℃, scattering carbomer, swelling, adding triethanolamine, neutralizing, stirring to form gel, and uniformly coating on a medical elastic sponge hemisphere of a quick-release region and a backing layer of a quick-release region, wherein the thickness is 3mm, and the area ratio of the quick-release region to the quick-release region is 2:3.
(3) Mixing ethyl cellulose and water-soluble pore-forming agent polyethylene glycol 400 (the ratio is 9:1), dissolving in 95% ethanol solution (the total mass concentration of the ethyl cellulose and the polyethylene glycol 400 is 50%), pouring into a mould, drying at 45 ℃ to obtain a pore-forming agent-containing ethyl cellulose film with the thickness of 2mm, cutting, and covering the film on diclofenac sodium gel in a drug release control region.
(4) The medical pressure sensitive adhesive is coated on the backing layer of the adhesive area.
(5) Cutting the protective film (release paper) into a shape matched with the abdomen navel patch body and covering the abdomen navel patch body to obtain the diclofenac sodium abdomen navel patch which is particularly suitable for pain relief after anorectal operation.
2. In-vitro release degree determination test and result of diclofenac sodium abdominal navel patch
According to general rule of IV transdermal patch of second appendix of 2015 edition of Chinese pharmacopoeia, the release characteristics of the abdomen-navel patch drug can be evaluated by an in vitro release degree measurement test, the specific method is carried out according to the fourth method (device of method 2) of dissolution degree and release degree measurement method of 0931 of fourth appendix of 2015 edition of Chinese pharmacopoeia, 500ml of physiological saline is used as a release medium, and the rotating speed is 50 r.min -1 Taking the abdomen navel patch, removing the protective film, placing between two layers of discs with the dissolution surface facing upwards, horizontally placing the net disc at the lower part of the dissolution cup, and enabling the net disc to be parallel to the rotation surface of the bottom of the oar, wherein the distance between the net disc and the rotation surface of the bottom of the oar is 25+/-2 mm. Taking 4ml of receiving solution at time points of 0h, 0.5h, 1h, 1.5h, 2h, 4h, 8h, 12h, 16h, 20h, 24h and 30h respectively, supplementing physiological saline with the same volume and temperature, measuring acetaminophen concentration by an ultraviolet spectrophotometer, measuring wavelength to 276nm, and calculating cumulative release degree according to the following formula: cumulative release (%) =t time the amount of drug released cumulatively/total amount of drug in the navel patch×100%.
The results of the in vitro release measurement test of diclofenac sodium navel patch are shown in table 2 and fig. 5.
Table 2: cumulative Release measurement result
| Sampling point numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
| Time (h) | 0 | 0.5 | 1 | 1.5 | 2 | 4 | 8 | 12 | 16 | 20 | 24 | 30 |
| Cumulative release (%) | 0 | 32.3 | 36.7 | 39.8 | 42.4 | 50.5 | 60.1 | 67.6 | 73.1 | 78.2 | 81.6 | 82.7 |
As is clear from the data and cumulative release profile in the table, the drug was released rapidly for the first 1 hour, the cumulative release reached 36.7% and then gradually slowed down to cumulative release of 42.4%, 50.5%, 60.1%, 67.6%, 73.1%, 78.2%, 81.6%, 82.7% for 2h, 4h, 8h, 12h, 16h, 20h, 24h, 30h, respectively, showing a uniform release profile. The ratio of the areas of the quick-release medicine area to the quick-release medicine area is 2:3, the thickness of the diclofenac sodium gel is the same (uniform coating), and the medicine contents of the quick-release medicine area and the quick-release medicine area are 40% and 60% respectively, so that the medicines in the quick-release medicine area basically permeate completely within 1 hour, the quick-release analgesic effect is exerted, then the medicine release speed in the quick-release medicine area is basically constant, the accumulated release degree reaches 81.6% until 24 hours, and the analgesic effect can be maintained for 24 hours.
Example 3
1. Preparation of diclofenac sodium abdominal navel plaster
(1) Cutting medical elastic sponge into hemispheres which can be matched with human navel by using a die, placing the hemispheres into coating liquid (the coating liquid is 95% ethanol solution of ethyl cellulose) for 3min, taking out, drying at 48 ℃ to obtain medical elastic sponge hemispheres with surfaces coated with nonporous ethyl cellulose films, and bonding the medical elastic sponge hemispheres on the middle positions of backing layers.
(2) The preparation method comprises the following steps of: 1.5% of diclofenac sodium, 1.2% of carbomer, 15% of propylene glycol, 1.2% of triethanolamine and the balance of distilled water, and the preparation steps are as follows: dissolving diclofenac sodium in a mixed solution of propylene glycol and distilled water, boiling, cooling to 65 ℃, scattering carbomer, swelling, adding triethanolamine, neutralizing, stirring to form gel, and uniformly coating on a medical elastic sponge hemisphere of a quick-release region and a backing layer of a quick-release region, wherein the thickness is 3mm, and the area ratio of the quick-release region to the quick-release region is 2:3.
(3) Mixing ethyl cellulose and water-soluble pore-forming agent polyethylene glycol 400 (the ratio is 9:1), dissolving in 95% ethanol solution (the total mass concentration of the ethyl cellulose and the polyethylene glycol 400 is 50%), pouring into a mould, drying at 48 ℃ to obtain a pore-forming agent-containing ethyl cellulose film with the thickness of 2mm, cutting, and covering the film on diclofenac sodium gel in a drug release control region.
(4) The medical pressure sensitive adhesive is coated on the backing layer of the adhesive area.
(5) Cutting the protective film (release paper) into a shape matched with the abdomen navel patch body and covering the abdomen navel patch body to obtain the diclofenac sodium abdomen navel patch which is particularly suitable for pain relief after anorectal operation.
2. In-vitro release degree determination test and result of diclofenac sodium abdominal navel patch
According to general rule of IV transdermal patch of second appendix of 2015 edition of Chinese pharmacopoeia, the drug release characteristics of the navel patch can be evaluated through an in vitro release degree measurement test, the specific method is carried out according to a fourth method (a method 2 device) of the four rule 0931 dissolution degree and release degree measurement method of 2015 edition of Chinese pharmacopoeia, 500ml of physiological saline is used as a release medium, the rotating speed is 50r & min < -1 >, the navel patch is taken, a protective film is removed, the protective film is placed between two layers of discs, the dissolution surface faces upwards, and the net disc is horizontally placed at the lower part of a dissolution cup, so that the net disc is parallel to the rotating surface of the bottom of a oar, and the distance between the net disc and the rotating surface is 25+/-2 mm. Taking 4ml of receiving solution at time points of 0h, 0.5h, 1h, 1.5h, 2h, 4h, 8h, 12h, 16h, 20h, 24h and 30h respectively, supplementing physiological saline with the same volume and temperature, measuring acetaminophen concentration by an ultraviolet spectrophotometer, measuring wavelength to 276nm, and calculating cumulative release degree according to the following formula: cumulative release (%) =t time the amount of drug released cumulatively/total amount of drug in the navel patch×100%.
The results of the in vitro release measurement test of diclofenac sodium navel patch are shown in table 3 and fig. 6.
Table 3: cumulative Release measurement result
| Sampling point numbering | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 |
| Time (h) | 0 | 0.5 | 1 | 1.5 | 2 | 4 | 8 | 12 | 16 | 20 | 24 | 30 |
| Cumulative release (%) | 0 | 34.2 | 39.8 | 43.1 | 45.4 | 51.4 | 60.3 | 67.3 | 74.1 | 78.9 | 82.3 | 83.3 |
As is clear from the data and cumulative release profile in the table, the drug was released rapidly for the first 1 hour, the cumulative release reached 39.8%, and then gradually slowed down to cumulative release of 45.4%, 51.4%, 60.3%, 67.3%, 74.1%, 78.9%, 82.3%, 83.3% for 2h, 4h, 8h, 12h, 16h, 20h, 24h, 30h, respectively, showing a uniform release profile. The ratio of the areas of the quick-release medicine area to the quick-release medicine area is 2:3, the thickness of the diclofenac sodium gel is the same (uniform coating), and the medicine contents of the quick-release medicine area and the quick-release medicine area are 40% and 60% respectively, so that the medicines in the quick-release medicine area basically permeate completely within 1 hour, the quick-release analgesic effect is exerted, then the medicine release speed in the quick-release medicine area is basically constant, the accumulated release degree reaches 82.3% until 24 hours, and the analgesic effect can be maintained for 24 hours.
Claims (4)
1. The utility model provides a diclofenac sodium abdomen navel subsides suitable for anus intestines postoperative analgesia which characterized in that: the abdomen navel patch comprises a back lining layer (5), an abdomen navel patch body and a protective film (1), wherein the abdomen navel patch body is covered on the back lining layer, and the protective film is covered on the surface of the abdomen navel patch body;
the abdomen navel patch body is sequentially provided with a quick medicine releasing area, a medicine controlling and releasing area and a pasting area from the center of the circle outwards;
the quick-release medicine region comprises a diclofenac sodium gel layer (2.1) and a medical elastic sponge (2.3) coated with a nonporous ethylcellulose film (2.2), wherein the diclofenac sodium gel layer is coated on the surface of the medical elastic sponge coated with the nonporous ethylcellulose film, and the medical elastic sponge coated with the nonporous ethylcellulose film is bonded on the back lining layer;
the quick-release medicine control region comprises a porous ethyl cellulose film layer (3.1) and a diclofenac sodium gel layer (3.2), wherein the porous ethyl cellulose film layer covers the surface of the diclofenac sodium gel layer, and the diclofenac sodium gel layer is coated on the back layer;
the pasting area is pressure sensitive adhesive (4);
the area ratio of the quick-release medicine region to the controlled-release medicine region is 2:3, a step of;
the medical elastic sponge is in a hemispheroidal shape;
the nonporous ethylcellulose film is made from an ethanol solution of 20wt.% ethylcellulose;
the diclofenac sodium gel layer is prepared from the following raw materials in percentage by weight: 0.5-2% of diclofenac sodium, 0.5-1.2% of carbomer, 6-20% of propylene glycol, 0.4-1.5% of triethanolamine and the balance of distilled water; the sum of the weight percentages of all the raw materials is 100 percent;
the porous ethyl cellulose membrane layer is prepared from an ethanol solution of ethyl cellulose and polyethylene glycol 400, the total mass concentration of the ethyl cellulose and the polyethylene glycol 400 is 50%, and the weight ratio of the ethyl cellulose to the polyethylene glycol 400 is 9:1.
2. The method for preparing diclofenac sodium navel patch suitable for anorectal postoperative pain relieving according to claim 1, which is characterized in that: the method comprises the following steps:
step 1, cutting a medical elastic sponge into a hemispherical shape matched with the navel of a human body, placing the hemispherical shape in an ethanol solution of 20wt.% ethyl cellulose, taking out the hemispherical shape, drying the hemispherical shape to obtain the medical elastic sponge coated with a nonporous ethyl cellulose film, and then bonding the medical elastic sponge on a backing layer;
step 2, dissolving diclofenac sodium in a mixed solution of propylene glycol and distilled water, boiling, cooling to 50-70 ℃, adding carbomer, swelling, adding triethanolamine to obtain diclofenac sodium gel, and coating the diclofenac sodium gel on the surface of a medical elastic sponge coated with a nonporous ethylcellulose film in a quick-release area and the surface of a backing layer in a quick-release area to form a diclofenac sodium gel layer;
step 3, mixing ethyl cellulose and polyethylene glycol 400, dissolving in 95% ethanol solution, pouring the mixed solution into a mold, drying to obtain a porous ethyl cellulose film, and covering the porous ethyl cellulose film on a diclofenac sodium gel layer in a drug release control region to form a porous ethyl cellulose film layer;
step 4, coating a pressure-sensitive adhesive on the backing layer to form a sticking area;
and 5, covering the protective film on the abdomen-navel paste body to obtain the diclofenac sodium abdomen-navel paste.
3. The preparation method according to claim 2, characterized in that: the thickness of the diclofenac sodium gel layer is 2-6mm.
4. The preparation method according to claim 2, characterized in that: the thickness of the porous ethyl cellulose film layer is 2mm.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5374661A (en) * | 1991-07-03 | 1994-12-20 | Sano Corporation | Composition and method for transdermal delivery of diclofenac |
| CN201564664U (en) * | 2009-04-14 | 2010-09-01 | 王凌峰 | Medicine navel pressing paste |
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2021
- 2021-03-24 CN CN202110312512.1A patent/CN112870180B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5374661A (en) * | 1991-07-03 | 1994-12-20 | Sano Corporation | Composition and method for transdermal delivery of diclofenac |
| CN201564664U (en) * | 2009-04-14 | 2010-09-01 | 王凌峰 | Medicine navel pressing paste |
Non-Patent Citations (3)
| Title |
|---|
| Transdermal patches: Design and current approaches to painless drug delivery;OTHMAN A. AL HANBALI et al；;《Acta Pharm.》;第69卷;197–215 * |
| 双氯芬酸制剂研究进展;宾驰;《现代中西医结合杂志》;第19卷(第23期);2983-2985 * |
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