Meloxicam cataplasm and preparation method thereof

Abstract

The invention belongs to the technical field of medicines, and discloses a meloxicam cataplasm and a preparation method thereof. The meloxicam cataplasm is composed of a backing layer, a paste layer and a protective layer, wherein the paste layer comprises an active component meloxicam, an adhesive, a humectant, a drug dissolution promoter, a transdermal enhancer, a surfactant, a pH regulator, a preservative and the balance of water for injection. The preparation method comprises the following steps: dissolving an adhesive, a transdermal enhancer and a preservative in water for injection, stirring and uniformly mixing to serve as a matrix phase; uniformly mixing the meloxicam with the humectant, adding the drug dissolution promoter and the surfactant to dissolve the active ingredients, and uniformly stirring to obtain a liquid medicine phase; the preparation method comprises the following steps: transferring a matrix phase and a liquid medicine phase into a closed vacuum tank, stirring and mixing in vacuum, adding a pH regulator, continuously stirring to obtain an ointment, uniformly coating a backing material with the ointment, covering the upper surface with a protective layer, and drying at low temperature to obtain the meloxicam cataplasm, which can relieve inflammation symptoms of soft tissue injury, such as pain, swelling and the like. The medicine is used for treating osteoarthritis.

Description

Technical Field

[0001] The invention relates to a transdermal drug preparation, belonging to the technical field of medicines, and in particular to a meloxicam palpable preparation and a preparation method thereof. Background Art

[0002] The mechanism of action of nonsteroidal anti-inflammatory drugs is to prevent the synthesis of inflammatory prostaglandins (PGs) and the like by inhibiting cyclooxygenase (COX). Cyclooxygenase (COX) is a membrane-bound serum protein and glycoprotein that catalyzes the oxidation of arachidonic acid (AA) to prostaglandin G2 (PGG2), and then reduces PGG2 to PGH2. COX has two isomers: cyclooxygenase-1 (COX-1)—constitutive enzyme and cyclooxygenase-2 (COX-2)—PGG2 inducible enzyme. The inducible enzyme COX-2 is induced by inflammatory regulation and is involved in the regulation of inflammatory responses; while the constitutive enzyme COX-1 is necessary for normal physiological processes and is present in most tissues. Its function is to synthesize PG to regulate the normal physiological activity of cells, protect the gastrointestinal mucosa, support microcirculation in the kidneys, and protect other organs from damage. Among many different nonsteroidal anti-inflammatory drugs (NSAIDs) that are selective inhibitors of cyclooxygenase (COX), meloxicam selectively inhibits COX-2, while diclofenac, piroxicam, indometacin and other NSAIDs either inhibit both COXs or inhibit COX-1 more strongly than COX-2. Meloxicam has better gastrointestinal safety and less renal toxicity, all due to its weak ability to inhibit COX-1.

[0003] Meloxicam is an enolic acid nonsteroidal anti-inflammatory drug (NSAID for short), which is very slightly soluble in methanol or ethanol and almost insoluble in water. It has strong analgesic and anti-inflammatory effects and a wide range of applications. It is mainly used in the treatment of osteoarthritis and rheumatoid arthritis in clinical practice. It only needs to be taken once a day, has a small dose (7.5-15 mg), and has a strong efficacy, which is superior to other nonsteroidal anti-inflammatory drugs. Its mechanism of action is to inhibit the synthesis of selective prostaglandins by inhibiting COX, and has a highly selective inhibitory effect on COX-2. COX has two isomeric forms: COX-1 and COX-2. The anti-inflammatory effect of NSAID is produced by the inhibition of COX-2, while the side effects are caused by the inhibition of COX-1. The smaller the required concentration ratio of NSAID to inhibit COX-2 and COX-1 (COX-2 / COX-1), the more COX-2 selective the product is. The COX-2 / COX-1 ratio of meloxicam is 0.33, that of diclofenac is 2.2, that of tenoxicam is 33, and that of indomethacin is 107.

[0004] At present, the pharmaceutical dosage form of meloxicam is mainly oral preparations, including tablets, capsules, dispersible tablets, injections, suppositories, gels, etc. Clinically verified, oral preparations have a small dose (7.5-15 mg / time / day), definite efficacy, and few side effects, but long-term use causes certain adverse stimulation to the gastrointestinal tract, such as nausea, vomiting, anorexia, gastric ulcers or duodenal ulcers. For patients with gastrointestinal diseases, it may cause acute gastroenteritis and gastric bleeding. Long-term or excessive use can lead to serious complications such as gastric ulcers, liver damage, and renal damage. Injections may also cause local pain and mild tissue necrosis at the injection site. Suppositories are rectal medications and should be used as short-term as possible, because after rectal administration and absorption, in addition to the possible side effects of oral administration, local toxic effects may also occur. Gels are administered frequently (3-4 times / day), and are easy to contaminate clothes, making them inconvenient to use.

[0005] Babu, also known as Babu ointment or gel patch, refers to a patch made by mixing raw drug with a suitable hydrophilic matrix and then coating it on a backing material. The drug is absorbed from the skin into the systemic blood circulation and reaches an effective blood concentration to achieve disease treatment or prevention. Babu can avoid the first-pass effect of the liver and the inactivation of the drug in the gastrointestinal tract. The absorption of the drug is not affected by gastrointestinal factors, reducing individual differences in medication. It can maintain a constant effective blood drug concentration or physiological effect, avoid the peak and valley phenomenon of blood drug concentration caused by oral administration, and reduce toxic and side effects. It can reduce the number of dosing times, improve therapeutic efficacy, prolong the duration of action, avoid multiple doses, and make it easy for most patients to accept. It is easy to use, and patients can take the drug independently or withdraw it at any time. It has strong targeting and can act directly on the patient to maximize the efficacy of the drug. It is moisturizing, breathable, aging-resistant, has a large drug loading capacity, and is non-irritating and non-allergenic. The viscosity is controllable and moderate, and it can be repeatedly peeled off and applied. Compared with traditional adhesive plasters and black plasters, the adhesive plasters have too strong adhesion to the skin, which will cause damage to body hair, difficulty in peeling, and cause pain to patients, and they are disposable. The black plaster must be heated when used, and it sticks to body hair and contaminates the skin, and it is difficult to clean after use. However, due to the adjustable viscosity and affinity, the poultice can achieve moderate adhesion to the human body, is easy to peel off, and can be repeatedly peeled off. Summary of the invention

[0006] The present invention provides a poorly soluble drug meloxicam palpable preparation, which solves the problem that meloxicam is insoluble in water and improves the stability of the poorly soluble drug meloxicam. The meloxicam palpable preparation has a large drug loading amount, a quick onset of effect, good transdermal absorption and good storage stability.

[0007] The problem to be solved by the present invention is mainly solved by providing the following technical solutions:

[0008] A meloxicam papule is composed of a backing layer, a paste layer and a protective layer. The paste layer is composed of the following components in percentage by weight: 1% to 2% of an active ingredient meloxicam, 5% to 25% of an adhesive, 20% to 50% of a moisturizer, 0.1% to 1% of a drug dissolution promoter, 0.5% to 2.5% of a transdermal enhancer, 0.1% to 2% of a surfactant, 2% to 5% of a pH regulator, 0.001% to 0.02% of a preservative and the remainder of water for injection.

[0009] The adhesive is selected from one or more of carbomer homopolymer, sodium carboxymethyl cellulose, povidone, polyvinyl alcohol, gelatin, methyl cellulose, tragacanth gum, gum arabic, peach gum, sodium polyacrylate, and agar.

[0010] The humectant is selected from one or more of polyethylene glycol, propylene glycol and glycerin.

[0011] The drug dissolution promoter is selected from one of sodium hydroxide and potassium hydroxide.

[0012] The transdermal enhancer is selected from azone.

[0013] The surfactant is selected from one or more of sodium dodecyl sulfate, sodium dodecylbenzene sulfonate, and polysorbate 80.

[0014] The pH regulator is selected from one of borate buffer, triethanolamine and phosphate buffer.

[0015] The preservative is selected from one or more of thimerosal, benzalkonium chloride, benzalkonium bromide, methylparaben and ethylparaben.

[0016] The meloxicam palpable preparation also contains a backing layer and a protective layer, wherein the backing material is selected from non-woven fabric or stretch fabric, and the protective layer is selected from one of polyvinyl chloride film, low-density polyethylene film, and biaxially stretched polypropylene film.

[0017] Furthermore, the present invention provides a method for preparing a meloxicam cataplasm, the specific steps of which are as follows:

[0018] (1) Add injection water to the adhesive and stir to swell it, dissolve and dilute the preservative with injection water (or ethanol) and then add it, then add the transdermal enhancer and stir evenly to form phase I (matrix phase);

[0019] (2) mixing the meloxicam raw material and the moisturizer evenly, adding the drug dissolving agent and the surfactant to dissolve the meloxicam raw material, and stirring and mixing evenly to form phase II (drug liquid phase);

[0020] (3) Phase I and Phase II are transferred to a sealed vacuum tank, stirred and mixed under vacuum, and then a pH adjuster is added to adjust the pH of the paste to 7.5-8.5. The mixture is stirred under vacuum until the paste has a uniform color to obtain a drug-containing paste. The drug-containing paste is evenly coated on a backing material, and a protective layer is added to the upper surface. The paste is cut into pieces with a size of 7×10 cm and dried at low temperature.

[0021] In step (3), the vacuum state is a vacuum degree not less than -0.08Mpa.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] (1) The present invention provides a solution to the problem that nonsteroidal anti-inflammatory drugs are poorly soluble in water. The content of the prepared poultice is evenly distributed, which can ensure continuous and long-term drug delivery to the lesion site, thereby significantly improving the transdermal absorption rate of meloxicam and achieving rapid, continuous and stable release of the active ingredient.

[0024] (2) The dosage of meloxicam palpable agent is fixed and safe and controllable.

[0025] (3) Meloxicam barb has a large drug loading capacity and high water content, which can easily soften the skin stratum corneum, facilitating the transdermal absorption of the drug. It also has good air permeability, and its adhesion to the skin and heat preservation are better than those of traditional plasters. It has low irritation to the skin and can be repeatedly peeled off and applied without contaminating clothes or leaving any residue. It is painless to peel off after use. Specific embodiments

[0026] The technical solutions in the embodiments of the present invention will be described clearly and completely below in combination with the embodiments of the present invention. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0027] The present invention provides a preparation process of meloxicam cataplasm, which comprises the following steps:

[0028] (1) 5-25% adhesive (one or more selected from carbomer homopolymer, sodium carboxymethyl cellulose, povidone, polyvinyl alcohol, gelatin, methyl cellulose, tragacanth gum, gum arabic, peach gum, sodium polyacrylate, agar) is added to water for injection and stirred to swell. 0.001-0.02% preservative (one or more selected from thimerosal, benzalkonium chloride, benzalkonium bromide, methylparaben, ethylparaben) is dissolved and diluted with an appropriate amount of water for injection (or ethanol) and then added thereto. Then, 0.5-2.5% transdermal enhancer (one or more selected from azone, borneol, menthol, ethanol) is added and stirred evenly to form phase I (matrix phase).

[0029] (2) The meloxicam raw material is mixed evenly with 20-50% of a humectant (one or more of polyethylene glycol, propylene glycol, and glycerin), and 0.1-1% of a dissolving agent (one of sodium hydroxide or potassium hydroxide) and 0.1-2% of a surfactant (one of sodium dodecyl sulfate, sodium dodecylbenzene sulfonate, and polysorbate 80) are added to dissolve the meloxicam raw material, and the mixture is stirred and mixed evenly to form phase II (drug liquid phase).

[0030] (3) Phase I and Phase II are transferred to a sealed vacuum stirring tank, stirred and mixed under vacuum (vacuum degree is not less than 0.08 MPa), and then 2-5% pH adjuster (one or more of borate buffer, triethanolamine, and phosphate buffer) is added to adjust the pH of the paste to 7.5-8.5, and the paste is stirred continuously under vacuum until the color of the paste is uniform to obtain a drug-containing paste, and the drug-containing paste is evenly coated on the backing material, and a protective layer is added on the upper surface, and the paste is cut into a size of 7×10 cm and dried at low temperature.

[0031] The following is a further description of a meloxicam palpable preparation and a preparation method thereof in conjunction with specific implementation examples. In the following embodiments, for the convenience of description, the backing material is non-woven fabric and the protective layer is polyvinyl chloride film.

[0032] Example 1

[0033] In preparation pot I, add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 2.8 kg of polyvinyl alcohol, 2.0 kg of povidone, 3.2 kg of tragacanth gum, and 2 kg of gelatin, and stir to make them completely swollen. Dissolve 0.02 kg of thimerosal in a small amount of water for injection, dissolve 2.0 kg of azone and 6 kg of ethanol, then add them together into preparation pot I and stir evenly to obtain phase I (matrix phase) for standby use.

[0034] In preparation pot II, add 15 kg each of glycerol and propylene glycol, add 1 kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6 kg of sodium hydroxide in water for injection), dissolve 0.3 kg of sodium lauryl sulfate in 2.5 kg of water for injection, then add it, stir to dissolve the meloxicam, and obtain phase II (liquid phase).

[0035] First, transfer phase I to a closed vacuum stirring tank, stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank, stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 4.0kg of borate buffer, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into a specification of 7×10cm, dry at low temperature, and make 10,000 patches.

[0036] Example 2

[0037] In preparation pot I, add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 2.8 kg of polyvinyl alcohol, 2.0 kg of gelatin, 2.0 kg of gum arabic, and 1.5 kg of sodium carboxymethyl cellulose, and stir to make them completely swollen. Dissolve 0.015 kg of benzalkonium chloride in a small amount of water for injection, dissolve 2.0 kg of azone and 6 kg of ethanol, then add them together into preparation pot I and stir evenly to obtain phase I (matrix phase) for standby use.

[0038] In preparation pot II, add 15 kg each of glycerol and polyethylene glycol 400, add 1 kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6 kg of sodium hydroxide in water for injection), dissolve 0.3 kg of sodium lauryl sulfate in 2.5 kg of water for injection, then add it, stir to dissolve the meloxicam, and obtain phase II (liquid phase).

[0039] First, transfer phase I to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 3kg of triethanolamine, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into 7×10cm specifications, dry at low temperature, and make 10,000 patches.

[0040] Example 3

[0041] In preparation pot I, add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 1.5 kg of sodium carboxymethyl cellulose, 2.8 kg of polyvinyl alcohol, 1.5 kg of povidone, 1.5 kg of peach gum, and 2.0 kg of methyl cellulose, and stir to completely swell. Dilute 200 ml of 5% benzalkonium bromide solution with a small amount of water for injection, dissolve 2.5 kg of azone and 6 kg of ethanol, and add them together to preparation pot I, stir evenly, to obtain phase I (matrix phase), and set aside.

[0042] In preparation pot II, add 13 kg each of propylene glycol and polyethylene glycol 200, add 1 kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6 kg of sodium hydroxide in water for injection), add 1 kg of polysorbate 80, stir to dissolve the meloxicam, and prepare phase II (liquid phase).

[0043] First, transfer phase I to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 4.8kg of phosphate buffer, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into 7×10cm specifications, dry at low temperature, and make 10,000 patches.

[0044] Example 4

[0045] Add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 2.8 kg of polyvinyl alcohol, 2.0 kg of methylcellulose, 1.5 kg of povidone, 2.0 kg of sodium polyacrylate and 1.5 kg of agar into preparation pot I, and stir to make them completely swollen. Dissolve 0.015 kg of methylparaben in a small amount of water for injection, dissolve 2.5 kg of azone and 6 kg of ethanol, then add them into preparation pot I together and stir evenly to obtain phase I (matrix phase) for standby use.

[0046] In preparation pot II, add 13 kg each of glycerol and polyethylene glycol 200, add 1 kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6 kg of sodium hydroxide in water for injection), add 1 kg of polysorbate 80, stir to dissolve the meloxicam, and prepare phase II (liquid phase).

[0047] First, transfer phase I to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 3.2kg of triethanolamine, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into a specification of 7×10cm, dry at low temperature, and make 10,000 patches.

[0048] Example 5

[0049] In preparation pot I, add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 2.5 kg of gelatin, 1.5 kg of sodium carboxymethyl cellulose, 1.5 kg of povidone, 2.5 kg of peach gum, and 2.0 kg of tragacanth gum, and stir to completely swell. Dissolve 0.015 kg of ethyl hydroxybenzoate and 2.5 kg of azone and 6 kg of ethanol, then add them together to preparation pot I and stir evenly to obtain phase I (matrix phase) for standby use.

[0050] In preparation pot II, add 13 kg each of propylene glycol and polyethylene glycol 600, add 1 kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6 kg of sodium hydroxide in water for injection), add 1 kg of polysorbate 80, stir to dissolve the meloxicam, and prepare phase II (liquid phase).

[0051] First, transfer phase I to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 3.2kg of triethanolamine, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into a specification of 7×10cm, dry at low temperature, and make 10,000 patches.

[0052] Example 6

[0053] In preparation pot I, add 30 kg of water for injection, 1.2 kg of carbomer homopolymer, 2.0 kg of sodium polyacrylate, 2.5 kg of gelatin, 2.0 kg of gum arabic, 1.5 kg of agar, and 2.0 kg of methylcellulose, and stir to completely swell. Add 6 kg of ethanol to 0.01 kg each of methylparaben and ethylparaben, dissolve them, and then add them to preparation pot I together, stir evenly, to obtain phase I (matrix phase), and set aside.

[0054] In preparation pot II, add 8kg of propylene glycol, 10kg of glycerol, 8kg of polyethylene glycol 400, and 1kg of meloxicam, stir evenly, add 8% sodium hydroxide solution (prepared by dissolving 0.6kg of sodium hydroxide in water for injection), dissolve 0.3kg of sodium lauryl sulfate in 2.5kg of water for injection, and add it therein, stir to dissolve the meloxicam, and obtain phase II (drug liquid phase).

[0055] First, transfer phase I to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 15 to 20 minutes, then transfer phase II to a closed vacuum stirring tank and stir under vacuum (vacuum degree not less than -0.08MPa) for 25 to 40 minutes, add 3.2kg of triethanolamine, make up the total weight to 100kg with water for injection, continue stirring under vacuum (vacuum degree not less than -0.08MPa) for 60 minutes to obtain a drug-containing ointment; evenly apply the drug-containing ointment on a non-woven fabric, cover the upper surface with a polyvinyl chloride film, cut into a specification of 7×10cm, dry at low temperature, and make 10,000 patches.

[0056] In order to confirm the anti-inflammatory effect of meloxicam palpable agent, we conducted pharmacological and toxicological tests and clinical trials with the samples prepared in Example 1. The specific test results are as follows.

[0057] 1. Safety evaluation

[0058] 1. Skin irritation test

[0059] This product was subjected to an irritation test on guinea pig skin. The results showed that no skin irritation reaction was observed on the normal skin and damaged skin of guinea pigs after using meloxicam palpable agent once or for seven consecutive days, indicating that meloxicam palpable agent has no obvious irritation reaction to the skin.

[0060] 2. Skin allergy test

[0061] This product was subjected to an allergy test on guinea pig skin, and the results showed that no allergic reaction was observed after repeated use of meloxicam palpable agent on the local skin of guinea pigs.

[0062] 2. Pharmacodynamics Study

[0063] 1. The results of the anti-inflammatory test on carrageenan-induced swelling of rat toes showed that meloxicam palpable agent had a significant inhibitory effect on the swelling of rat toes 1 hour after carrageenan induced inflammation, and the effect lasted until 24 hours after inflammation.

[0064] 2. The results of the test on the preventive effect on adjuvant arthritis in rats showed that meloxicam palpable agent had a significant inhibitory effect on the swelling of adjuvant arthritis in rats three days after preventive administration. Seven days after preventive administration, the swelling inhibition rates were 62.15%, 65.07% and 68.54%, respectively.

[0065] 3. The results of the test on the therapeutic effect of adjuvant arthritis in rats showed that meloxicam palpable agent had a significant inhibitory effect on the swelling of adjuvant arthritis in rats after three days of treatment. The swelling inhibition rates after seven days of treatment were 37.57%, 51.18% and 59.82% respectively.

[0066] The results of pathological histological examination showed that meloxicam cataplasm relieved the inflammatory response of the ankle joints of rats with adjuvant arthritis to a certain extent, and had no significant effect on the weight and pathological histology of the thymus and spleen of rats with adjuvant arthritis. The anti-inflammatory effect of meloxicam cataplasm on animal inflammation models was similar to that of piroxicam.

[0067] 3. Clinical Trials

[0068] 1. Treatment of osteoarthritis (OA): The meloxicam palpable preparation developed by our unit was studied in a multicenter, randomized, double-blind, parallel controlled trial in three hospitals including the First Affiliated Hospital of Nanjing Medical University. The control drug was piroxicam gel. 45 patients with knee osteoarthritis were treated with meloxicam palpable preparation once a day. After 14 days of treatment, pain, swelling, tenderness (touch, percussion), limitation of daily activities, knee squatting, and total score of symptoms and signs were significantly improved. The total effective rate was 83.42%. There was no significant difference between the experimental group and the control group (81.82%).

[0069] 2. Treatment of acute soft tissue injury: The meloxicam barbu formulation developed by our unit was studied in a multicenter, randomized, double-blind, parallel controlled trial in three hospitals including the First Affiliated Hospital of Nanjing Medical University. The control drug was piroxicam gel. After using meloxicam barbu formulation, 42 patients with acute soft tissue injury showed significant improvement in pain, swelling, tenderness (touch, percussion), limitation of daily activities, active range of motion of joints, and total scores of symptoms and signs. The total effective rate was 97.26%. There was no significant difference between the experimental group and the control group (93.89%).

[0070] 3. Adverse reactions in clinical application: The meloxicam cataplasm developed by our unit was clinically verified in 139 patients with knee osteoarthritis and acute soft tissue injury in three hospitals including the First Affiliated Hospital of Nanjing Medical University. The treatment course was 14 days. The control drug was piroxicam gel. No local or systemic adverse reactions were found after using the test drug and the control drug. There was no significant change in blood routine, urine routine, liver and kidney function in the two groups of patients after medication. All groups of patients showed good tolerance.

[0071] Through safety evaluation, pharmacodynamic research and clinical trials of meloxicam palpable preparations, it is believed that meloxicam palpable preparations can relieve the inflammatory symptoms, pain, swelling, etc. of soft tissue injuries, and can be used for the treatment of osteoarthritis with good efficacy and high safety.

[0072] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements or modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A meloxicam palpable preparation, characterized in that: The invention is composed of a backing layer, a paste layer and a protective layer. The paste layer is composed of the following components in weight percentage: 1% to 2% of the active ingredient meloxicam, 5% to 25% of an adhesive, 20% to 50% of a moisturizer, 0.1% to 1% of a drug dissolution promoter, 0.5% to 2.5% of a transdermal enhancer, 0.1% to 2% of a surfactant, 2% to 5% of a pH regulator, 0.001% to 0.02% of a preservative and the remainder of water for injection.

2. The meloxicam cataplasm according to claim 1, characterized in that The adhesive is selected from one or more of carbomer homopolymer, sodium carboxymethyl cellulose, povidone, polyvinyl alcohol, gelatin, methyl cellulose, tragacanth gum, gum arabic, peach gum, sodium polyacrylate and agar.

3. The meloxicam cataplasm according to claim 1, characterized in that The moisturizing agent is selected from one or more of polyethylene glycol, propylene glycol and glycerin.

4. The meloxicam cataplasm according to claim 1, characterized in that The drug dissolution promoter is selected from one of sodium hydroxide and potassium hydroxide.

5. The meloxicam cataplasm according to claim 1, characterized in that: The transdermal enhancer is azone.

6. The meloxicam cataplasm according to claim 1, characterized in that: The surfactant is selected from one or more of sodium dodecyl sulfate, sodium dodecylbenzene sulfonate and polysorbate 80.

7. The meloxicam cataplasm according to claim 1, characterized in that: The pH regulator is selected from one of borate buffer, triethanolamine and phosphate buffer.

8. The meloxicam cataplasm according to claim 1, characterized in that: The preservative is selected from one or more of thimerosal, benzalkonium chloride, benzalkonium bromide, methylparaben and ethylparaben.

9. The meloxicam cataplasm according to claim 1, characterized in that: The backing material is selected from non-woven fabric or elastic fabric, and the protective layer is selected from one of polyvinyl chloride film, low-density polyethylene film and biaxially stretched polypropylene film.

10. The method for preparing the meloxicam cataplasm according to any one of claims 1 to 9, characterized in that: The steps are: (1) First, swell the adhesive with injection water, dissolve the transdermal enhancer with ethanol, dissolve the preservative with injection water and then add them into the adhesive, stir and mix them, and form phase I, i.e., matrix phase; (2) mixing the active ingredient meloxicam and the moisturizer, adding a drug dissolving agent and a surfactant to dissolve the active ingredient meloxicam, and stirring evenly to form phase II, i.e., the drug liquid phase; (3) Transfer phase I and phase II to a sealed vacuum tank, stir and mix them under vacuum, add a pH adjuster to adjust the pH of the paste to 7.5-8.5, and continue stirring under vacuum until the paste has a uniform color to obtain a drug-containing paste. The paste is evenly coated on the backing material, and a protective layer is added to the upper surface, cut, and dried at low temperature. Meloxicam palpable preparation was obtained.