JP2945344B2 - Edema rate reducing agent and edema suppression rate improving agent - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to the edema rate reduction enhancing agent consisting of di-hydroxy aluminum aminoacetate
And edema suppression rate-enhancing enhancer, and containing these
That relates to the edema rate reducing agent and edema inhibition rate improver.

[0002]

2. Description of the Related Art Indomethacin, ketoprofen and flurbiprofen are widely used in the field of orthopedic surgery for internal use in the treatment of osteoarthritis, shoulder periarthritis, muscle pain, etc.
Excellent effects have been observed.

On the other hand, in recent years, in order to prevent gastrointestinal disorders which are a side effect of these components, liquid preparations containing these components,
Ointments and patches have been developed. (JP-A-53-81
616, JP-A-56-135414, JP-A-57-35
509, JP-A-58-83621 and JP-A-58-396.
16, JP-A-55-62013, JP-A-55-6201
4, JP-A-57-140711, JP-A-61-2752
12, JP-A-63-88125). However, these components are poorly absorbed from the skin, and at present it is not possible to obtain a therapeutic effect higher than that of internal administration by topical administration, and improvement of the therapeutic effect by improving absorption from the skin was the biggest issue. .

As a method for solving this problem, a method for improving the solubility of these components in a base (Japanese Patent Application Laid-Open No.
36411, JP-A-58-124716, JP-A-58-124
4713, JP-A-59-137412, JP-A-61-1
2614, JP-A-62-270524), and a method of blending a component that promotes absorption from the skin (JP-A-58-150).
508, JP-A-58-52216, JP-A-60-146
823, JP-A-61-172833, JP-A-61-19
4015), a method of appropriately moisturizing the skin to promote absorption (JP-A-56-51412, JP-A-59-2797).
8) are known. However, these methods also promote the transfer of indomethacin, ketoprofen and flurbiprofen to the epidermis, but not to blood, muscle and synovial fluid. is not.

[0005]

DISCLOSURE OF THE INVENTION The present invention relates to an edema rate reduction and an edema rate reduction effect having a relatively early edema rate reduction effect and suppression rate improvement effect when applied or affixed to an inflamed affected area.
Strong agents and edema suppression rate enhancers, and
It is intended to provide an edema rate-reducing agent and an edema suppression rate-improving agent .

[0006]

SUMMARY OF THE INVENTION The present inventors have found that, based on the experimental results of an external anti-inflammatory analgesic containing indomethacin, ketoprofen and flurbiprofen, dihydroxyaluminum aminoacetate was contained in the plaster, and that The present inventors have found that the edema rate is reduced and the suppression rate is improved when the composition is applied or adhered to the present invention, and the present invention has been completed.

[0007] The present invention relates to an edema rate-reducing enhancer or edema inhibitor comprising dihydroxyaluminum aminoacetate.
Provide an efficiency enhancing enhancer. The present invention further relates to India
From Methacin, Ketoprofen and Flurbiprofen
At least one non-steroidal anti-inflammatory agent selected;
Dihydroxyaluminum aminoacetate in plaster
Edema rate reducing agent or edema suppression rate improving agent contained in
provide.

[0008]

BEST MODE FOR CARRYING OUT THE INVENTION The agent for reducing edema rate according to the present invention or
The edema suppression rate improving agent is obtained by mixing dihydroxyaluminum aminoacetate in a plaster body. The amount of the dihydroxyaluminum aminoacetate according to the present invention is not particularly limited, but is preferably about 0.2% by weight. In a further preferred form of the present invention, dihydroxyaluminum aminoacetate is added to the plaster, and at least one non-steroidal anti-inflammatory agent selected from indomethacin, ketoprofen and flurbiprofen is added to the paste.
1 to 5.0% by weight. Floating of the invention
Tumor rate reduction, or edema inhibition rate enhancers, by blended with dihydroxy aluminum aminoacetate in plaster, has a reducing effect or suppression rate enhancing effect edema rate.
Here, the edema rate E (%) refers to an edema rate reducing agent at a site where an inflammatory agent such as carrageenin is injected subcutaneously to cause inflammation.
Alternatively, an edema suppression rate improver is applied, and the site volume (Vn) immediately after injection of the proinflammatory agent and the site volume (V
t) is measured and E (%) = volume increase rate calculated by the formula of (Vt−Vn) / Vn × 100. In addition, suppression rate I (%)
Refers to the edema rate (E) of the test drug group in which the edema rate reducing agent or the edema suppression rate improving agent was applied to the site of inflammation after a predetermined time period
t) and the edema rate (Ec) of the control group to which the edema rate-reducing agent or the edema suppression rate-improving agent is not applied after a lapse of a predetermined time, calculated by the following formula: I (%) = (Ec−Et) / Ec × 100 Value. The edema rate-reducing agent of the present invention or
The edema-suppressing rate-improving agent reduces the edema at the site of inflammation by applying it to the site where the inflammation agent was injected (the site of inflammation). The edema rate is lower and the suppression rate is higher compared to an external anti-inflammatory analgesic that is not blended.
Therefore, the edema rate-reducing agent or the edema suppression rate-improving agent of the present invention suppresses edema in the affected area, and has an excellent edema rate-reducing effect or edema suppression effect due to a synergistic effect with a nonsteroidal anti-inflammatory agent.
The effect of the rate improver is exhibited.

[0009] The edema rate reducing agent or edema inhibition rate of the present invention
The upper preparation can be used in any dosage form as long as it is an external preparation, but in order to make the present invention more effective, it is preferably used for a patch. This patch can contain a plaster, dihydroxyaluminum aminoacetate, and various compounding components other than at least one nonsteroidal anti-inflammatory agent selected from indomethacin, ketoprofen and flurbiprofen.

In the case of a patch, an adhesive polymer, a humectant, a curing agent, an inorganic powder, a surfactant, water and the like are used.
Adhesive polymers include polyacrylic acid, sodium polyacrylate, gelatin, pectin, polyvinylpyrrolidone, vinyl acetate copolymer, polyethylene oxide, methyl vinyl ether / maleic anhydride copolymer,
Sodium alginate, sodium carboxymethylcellulose, xanthan gum, gum arabic, tragacanth gum and the like are used. As the humectant, glycerin, sorbitol, propylene glycol, polyethylene glycol, polypropylene glycol and the like are used.
As a curing agent, potassium aluminum sulfate, magnesium aluminate silicate, aluminum hydroxide, magnesium aluminate hydroxide, magnesium aluminate metasilicate, synthetic hydrotalcite, triglycidyl isocyanate, polyethylene glycol diglycidyl ether,
Ethylene glycol diglycidyl ether, glycerin diglycidyl ether, triglycerin diglycidyl ether and the like are used. Incidentally, dihydroxyaluminum amino acetate may be used in combination as a curing agent.
As the inorganic powder, kaolin, silicic anhydride, zinc oxide, titanium oxide or the like is used. As the surfactant, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene glycol ether, polyoxyethylene alkylphenyl ether, polyoxyethylene polyoxypropylene Examples thereof include alkyl ether, polyoxyethylene phytosterol, sorbitan fatty acid ester, and glycerin fatty acid ester.

The edema rate reducing agent or edema inhibition rate of the present invention
The upper agent may contain capsaicin and / or vanillyl amide nonylate. In this case, a synthetic product is used as the nonylate vanillylamide, and a synthetic product, a crude drug extract, or a crude drug powder or a crude drug extract or a crude drug tincture containing capsaicin may be used as capsaicin. The amount of these components is preferably 0.001 to 0.1% by weight in the case of nonylate vanillylamide. In the case of capsaicin, a synthetic product, a crude drug extract, 0.001 to
0.1% by weight of crude drug powder containing capsaicin is 0.1% by weight.
5 to 10% by weight, crude drug extract is preferably 0.01 to 1.0% by weight, and crude drug tincture is preferably 0.1 to 10% by weight. When the amount is less than this amount, improvement of the therapeutic effect by capsaicin and / or nonylate vanillylamide is small, and
If the amount is more than this, skin irritation such as redness and itching of the skin occurs, which is not preferable.

Further, the edema rate reducing agent or edema of the present invention
For the purpose of improving the efficacy and the feeling of use, various types of left-hand drugs such as l-menthol, dl-
Various stabilizers such as sodium edetate, sodium sulfite, butylhydroxyanisole, butylhydroxytoluene and the like can be compounded for the purpose of stabilizing the active ingredient such as camphor, tocopherol acetate, psyllium extract, sea chimney extract and arnica tincture.

[0013]

According to the present invention, an edema rate-reducing enhancer having a low edema occurrence and a high inhibitory effect or an edema suppression rate is improved.
A chemical enhancement agent is obtained. In addition, the composition containing at least one non-steroidal anti-inflammatory agent selected from indomethacin, ketoprofen and flurbiprofen has a low edema occurrence and a high inhibitory effect, and the non-steroidal anti-inflammatory agent absorption and by enhancing the transition to deep skin, floating the therapeutic effect is remarkably improved in
An agent for reducing tumor rate or improving the rate of suppressing edema is obtained.

[0014]

Examples (Products 1 to 5 of the present invention) The composition shown in Table 1 was prepared, and the edema rate was reduced and the edema inhibition rate was reduced.
An improved patch was used.

[Table 1]

(Comparative Examples 1 and 2) As shown in Table 2, a composition containing no dihydroxyaluminum aminoacetate was prepared to give an external anti-inflammatory analgesic patch.

[Table 2] Dissolve indomethacin, 1-menthol, dl-camphor, castor oil and POE (10) nonylphenyl ether. Next, dissolve the other ingredients, was dispersed, added indomethacin solution, those kneaded, and spread so that on the polyester nonwoven fabric 1 m ² per the 1000 g, this
These patches were prepared .

The edema rate and the inhibition rate of the inventive products 1 to 5 containing dihydroxyaluminum aminoacetate were determined and compared with Comparative Examples 1 and 2. The test method was as follows. A test drug (patch 3 × 3.5 cm was applied) was administered to a male Wistar rat (Charles River Japan), 6-week-old, right foot.
After 1 hour, 1% carrageenan (LAMBA CARRAGEENIN, Minsei R
Immediately after 0.1 ml of the ikagaku Co) solution was injected subcutaneously into the right foot, the volume was immediately measured with a volume measuring device (Ugo Basile). 2,
After 4 and 6 hours, the same operation was performed, and the edema rate and the inhibition rate were calculated from the following equations. The patch had to be peeled off each time to measure its volume, and it was difficult to use the same medicine repeatedly. Therefore, the patch was replaced with a new medicine every hour. Edema rate E (%) = (Vt−Vn) / Vn × 100 Vt: Footpad volume t hour after carrageenin injection Vn: Footpad volume immediately after carrageenin injection Inhibition rate I (%) = (Ec−Et) / Ec × 100 Et: Edema rate after t hours of test drug group Ec: Edema rate after t hours of control group

The evaluation results are shown in Tables 3 and 4. Table 3
As apparent from FIGS. 4 and 4, the product of the present invention containing dihydroxyaluminum aminoacetate has a lower edema rate and a higher suppression rate than untreated and Comparative Examples 1 and 2 containing no dihydroxyaluminum aminoacetate. It was confirmed that.

[Table 3]

[Table 4]

(Embodiment) 1. In the plaster, a) dihydroxyaluminum amino acetate and b) at least one nonsteroidal anti-inflammatory agent selected from indomethacin, ketoprofen and flurbiprofen 0.1 to 5.0% by weight. A patch that reduces the edema rate and improves the edema suppression rate . 2. A) dihydroxyaluminum aminoacetate; b) 0.1 to 5.0% by weight of at least one nonsteroidal anti-inflammatory agent selected from indomethacin, ketoprofen and flurbiprofen; c. ) An edema rate-reducing and edema-inhibiting rate-improving patch comprising 0.001 to 0.1% by weight of capsaicin and / or nonylate vanillylamide.

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁶ identification code FI A61K 31/19 602 A61K 31/19 602 31/405 31/405 (58) Fields surveyed (Int.Cl. ⁶ , DB name) A61K 31/58 A61K 9/06 A61K 9/70 A61K 31/19 A61K 31/405 CA (STN) MEDLINE (STN)

Claims (4)

(57) [Claims] An edema rate-reducing enhancer comprising dihydroxyaluminum aminoacetate . 2. Dihydroxyaluminum aminoacete
Edema suppression rate enhancer comprising 3. Indomethacin, ketoprofen and fumed
At least one non-sterol selected from lurbiprofen;
Lloyd anti-inflammatory and dihydroxy aluminum amino
An edema rate reducing agent comprising acetate in a plaster. 4. Indomethacin, ketoprofen and fumed
At least one non-sterol selected from lurbiprofen;
Lloyd anti-inflammatory and dihydroxy aluminum amino
Improvement of edema suppression rate by containing acetate in plaster
Agent.