JP3143885B2 - Oxicam transdermal formulation - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention
m) transdermal preparation ”is 0.1 to 50% oxicam, 0.1%
It is an anti-inflammatory transdermal absorption agent prepared by containing up to 70% of a Chinese medicine ingredient "promoting agent" and a necessary transdermal absorption excipient, and can improve gastrointestinal disorders as a side effect of the drug.

[0002]

2. Description of the Related Art Clinically usable non-steroidal anti-inflammatory drugs are classified into carboxylic acids (Ca-rboxylic acids) and enolic acids (Enolic acids) according to their chemical structures. Carboxylic acid nonsteroidal anti-inflammatory drugs are easily metabolized in the body or are rapidly excreted in urine by binding to glucuronic acid. For this reason, the blood half-life of such nonsteroidal anti-inflammatory drugs is very short. Among them, anti-inflammatory drugs containing an oxicam structure are frequently used because they are rapidly absorbed into the body, have a slow hepatic metabolic rate, and have a low renal excretion rate. Also, piroxicam has fewer side effects among this class of non-steroidal anti-inflammatory drugs. Oxicam anti-inflammatory drugs include isoxicam, sudoxicam, piroxicam,
Synoxicam, tenoxicam, romoxicam and the like are included. These anti-inflammatory and antipyretic analgesics are classified as non-narcotic analgesics because they have analgesic or anti-inflammatory properties and do not have the side effects seen in anesthesia such as respiratory depression and habits. . This kind of drug has the effect of relieving mild to moderate pain, suppressing the rise in body temperature, reducing inflammation, and preventing or alleviating gout, and has a very wide range of clinical applications.

[0003] The bioavailability of piroxicam was determined by Dr. 1981.
As reported by Brogden N. R. in Vol. 22, pp. 165-187, it has linear pharmacokinetic properties, and its blood maximum concentration (Cmax) and curve are independent of administration of single or multiple drugs. Lower area (A
UC) is directly proportional to dose. As a result of oral administration, anal administration and intravenous injection administration to mice and rabbits, oral administration is almost completely absorbed. It is also known that weakly acidic piroxicam exhibits a non-dissociated state in the stomach. Be
nveniste C. et al., 1985, Eur. J. Clin. Pha-rmacol.
According to the report in Vol. 38, pp. 547 to 549, the blood concentration peaks 2 hours after oral administration, and a second peak appears 12 hours after enterohepatic circulation.

[0004] In recent years, studies have been conducted to improve shortcomings such as initial transient effects and gastrointestinal disorders and reduce changes in blood concentration by adopting absorption routes other than the gastrointestinal tract and liver in a pharmaceutical formulation. Among them, the transdermal drug delivery system (dermal DDS) releases the drug continuously, is absorbed from the epidermis into the capillaries, reaches the therapeutic target through the circulatory system, and can achieve the therapeutic purpose. The risk of sudden release of drugs can be prevented, and the total area of ordinary adults is 2m ²
Thus, many capillaries are distributed, and the transdermal drug delivery system can quickly obtain a therapeutic effect.

[0005] Transdermal DDS is characterized by its physical properties such as distribution coefficient, molecular weight, concentration, molecular polarity, etc., base polarity, solubility of drug in the base, composition in the system, and base viscosity. Chemical properties, stratum corneum storage effect, skin surface lipid membrane, skin moisture retention (Hydration condition),
It is affected by skin physiology and pathological conditions such as skin temperature, patch site, skin trauma, pathological disorders, and drug metabolism in the skin. The problem currently faced by transdermal DDS is the lack of powerful and safe transdermal absorption enhancers.

[0006]

SUMMARY OF THE INVENTION It is an object of the present invention to provide an anti-inflammatory, antipyretic analgesic percutaneous absorbent containing a conventional Chinese medicine component "promoter", in which 0.1 to 50% of anti-inflammatory is contained. , Antipyretic analgesic, 0.1-70% Chinese medicine ingredient "enhancer",
It should contain the necessary transdermal absorption excipients.

[0007]

According to the present invention, an oxicam (Ox
icam) contains 0.1-50% of an anti-inflammatory, antipyretic analgesic, 0.1-70% of a Chinese herbal component "accelerator", and necessary transdermal absorption excipients. As shown in Tables 1-2, the content of the above-mentioned excipients is 0.01-99.95%, which is CMC Na and ethylene glycol. The preparations made in the present invention include ointments,
Includes suspensions, gels, solutions, emulsions, lotions, patches and sprays. The anti-inflammatory and antipyretic analgesic which is the main component of the present invention is an anti-inflammatory and antipyretic analgesic having an oxicam structure. Its structure is shown in FIG. 1 and includes piroxicam, sudoxicam, tenoxicam, isoxicam, cinoxicam, and romoxicam. Among them, more suitable compounds are piroxicam, isoxicam and tenoxicam.

[0008]

DETAILED DESCRIPTION OF THE INVENTION The in vitro percutaneous penetration test method employed in the present invention includes a conventional percutaneous absorption device (MANUAL) and an automatic percutaneous absorption device (AUTO-UV). As shown in FIG. 2, a conventional percutaneous absorption device is a vertical percutaneous permeation tank (Franzce).
ll), whose structure is a set of upright, double-walled glass containers that can be disassembled up and down. The lower vessel is filled with 0.2 M phosphate buffer and a stirrting bar is placed at the bottom to create a stirring effect of 600 rpm. Water is circulated through the layer between the inner and outer walls to maintain a constant temperature. In the upper container
Place 0.5 ml or 0.5 g of test product in different dosage forms. The top opening is covered with wrap. The skin of the experimental animal is sandwiched between the upper and lower layers. Rabbit abdominal skin, nude mouse abdominal skin and human lower leg skin are used as penetration barriers and fixed with metal clips. Periodically remove 200 μl of the phosphate buffer sample from the sample outlet and immediately add the same amount of phosphate buffer into the container to keep the solution volume constant. The sample taken out each time is calculated based on the content of the test product analyzed by high-pressure chromatography, using 100 μl × 30 μg / ml of isoxicam as a reference, and the permeation amount of the drug is calculated by a calibration curve to judge the degree of release of the preparation.

The automatic percutaneous absorption apparatus (AUTO-UV) comprises the above-mentioned conventional percutaneous absorption apparatus and an ultraviolet fluidized tank. The percutaneous permeation tank is a set of upright, two-layer Teflon containers that can be separated into upper and lower parts. The bottom container is connected to a multi-channel cassette pump, and a certain amount of 30% DMSO
The phosphate buffer solution is circulated between the percutaneous permeation tank and the ultraviolet fluidization tank. Computer regularly measures UV absorbance,
Record and calculate the results. The percutaneous penetration bath is kept in a stainless steel bath at 32 ° C. 0.5 ml on top of container
Place 0.5 g samples of different dosage forms and cover the top opening with wrap. Each experiment determines the UV absorbance criterion with one set of blank measurements.

In the present invention, different types of anti-inflammatory and antipyretic analgesics are used for the same type as the piroxicam structure.
Accelerators of different concentrations of Chinese herbal ingredients (hereinafter referred to as
(Referred to as “promoter” in Chinese herbal medicine) and used as a transdermal absorption enhancer. As shown in Table 3, the so-called Chinese medicine component “promoter” includes oleanolic acid, glycirizine, β-mi
Lucene, trans-cinnam aldehyde, cineau
Re, betulin, pinene, digitonin, ursolic acid
Selected from one or more of the Chinese herbal medicine ingredients
Shall be Each of these components can be
Exists. For example, pinene exists in eucalyptus, and its structure is classified into α-type and β-type. According to reports, there are (-)-α, (+)-α, (−)-β, and (+)-β, respectively, and only one of them is included in the drug material. In addition, different forms of pinene may be included. Yoshikone,
Herbal medicines, such as whitish and magnolia, include α-type and β-type.
Chinese herbal medicines such as saishin and pepper include β-form, and Chinese herbal medicines such as Shiso leaf, light load and ginger include α-form. Ascarensis,
(-)-Α type, (+)-α type and (+)-β type,
Including (+)-α type. Trans-cinnam aldehyde is present in cinnamon. Cineole is found in ginger, small gizzards, whites, eucalyptus, fists, and gejutsu. In terms of structure, they are classified into 1,8-structures and 1,4-structures. The 1,8-structure is present in whitish, small globules, eucalyptus and fist, while the 1,4-structure is present in each case. Glyciridin is present in licorice. Milsen is whitish , present in hops and the like. There is a β type in its structure,
β-type is present in ginger. Oleanoic acid is Renkyo
Nshyuyu, choji, present in large jujube. Betulin is a bellflower
Exists. Digitonin is present in digitalis leaves.

According to the present invention, various Chinese herbal components "promoter" are added based on CMC Na and ethylene glycol.
% Piroxicam gel on nude mouse abdominal skin
An in vitro percutaneous absorption penetration test was performed. Table 4 shows the amount of permeation accumulated per unit area after 72 hours. Control group without inakaru herbal medicine ingredient "enhancer" (G1)
3 to 5 are shown in FIGS. The formulation with terpineol showed the highest transdermal absorption effect. The penetration promoting effect of the 20% terpineol prescription group (G16) was 27.6 times that of the control group. Next, 10% terpineol prescription group
(G11) 25.9 times of control group, 15% terpineol prescription group (G13) 25.4 times of control group, 10% β
-The mixed formulation of myrcene and the same amount of terpineol (G12) was 22.6 times that of the control group. The permeation amount per unit area of the preparation was 259.3 μg / g in the control group (G1).
cm ² , G16: 7160.1 μg / cm ² , G11: 6716.2 μg / cm
² , G13: 6574.2 μg / cm ² , G12: 5846.9 μg / cm ²
Met.

The effect of the concentration of the "promoter" on transdermal absorption of piroxicam gel containing the same Chinese herbal component "promoter" is shown in FIGS. β-myrcene was used as an “accelerator” and the permeation amount per unit area of the G10 formulation containing 15% was 1977.5 μg / cm ^2, which was 259.
There is a 7.6-fold promotion effect compared to 3 μg / cm ² . Also,
G16 with 20% terpineol is 27.6 times faster. FIG. 8 shows the promoting effect on the abdominal skin of nude mice with respect to G11 of a single “promoting agent”, 10% terpineol formulation. Formulation G combined with other "accelerators"
A higher promotion effect is seen compared to 12. The results of the permeation test of the rabbit abdominal skin are shown in Table 5 and FIGS. 72
As for the cumulative amount of permeation per unit area after time, the terpineol-prescribed one showed the highest transdermal absorption effect as compared with the control group (G1) containing no “promoter”. 20%
The penetration promoting effect of the terpineol prescription group (G16) was 153.6 times that of the control group. Next, the 30% terpineol prescription group (G32) was 149.7 times the control group and 10%
Terpineol prescription group (G11) was 128
The mixed prescription of 10% terpineol and 15% β-myrcene (G18) was 116.9 times that of the control group, and the mixed prescription of 10% terpineol and 10% β-myrcene (G12) was 77.5 times that of the control group. The permeation amount per unit area of the preparation was 48.2 μg / cm ² in the control group (G1).
16, 7591.6 μg / cm ² , G32, 7211 μg / cm ² , G11
6165.2 μg / cm ² , G18 5563 μg / cm ² , G12 373
0.8 μg / cm ² .

FIG. 12 shows the effect on the transdermal absorption of the piroxicam gel containing the same Chinese herb component "promoter" by the change in the concentration of the "promoter". Terpineol is used as an "accelerator", and the G16 formulation containing 20% has a permeation amount per unit area of 153.6 times that of the control group (G1). G32 with 30% terpineol is 149.
It has 7 times the promotion effect. In addition, a single "accelerator" 10%
As for G11 of the terpineol formulation, the promotion effect on rabbit abdominal skin is higher than that of the formulation G12 or G18 combined with other “promoter” as shown in FIG. The effect of the change in the concentration of piroxicam in the gel on transdermal absorption is shown in Table 6 and FIG. 5
% Piroxicam G25 formulation has a penetration rate of 9 per unit area
6.1 μg / cm ² , 45.2 μg of control group (G1)
/ Cm ² , which was twice as effective. Also, the G23 formulation of 2% piroxicam has a permeation amount of 61.8 μg / cm ² and is 1.
It showed a 6-fold promotion effect. In addition, different receiving phases (Acc
The effect of the epting phase on the percutaneous penetration of piroxicam was investigated. A permeation test was performed on rabbit abdominal skin using a phosphate buffer solution containing 20% terpineol formulation (G16) and a buffer solution having a pH of 7.4 and a buffer solution of 30% DMSO. The result is shown in FIG.
As shown in Table 2, there was no statistically significant difference in the osmotic effect between the formulation G1 (the receiving phase was a phosphate buffer having a pH of 7.4) and G16 regardless of whether it contained 30% DMSO.

The results of the permeation test on the skin of the lower leg of a human are shown in Table 7 and FIG. G16 containing 20% terpineol showed the highest transdermal absorption effect. The amount of permeation per unit area was smaller for G16 than for the control group (G1), 8.8 μg / cm ^2.
18.4 times at 161.4 μg / cm ² , G12 at 110.2 μg / cm ²
It was 12.5 times and G8 was 6.3 times at 55.1 μg / cm ² . In addition, a single "accelerator" 20% terpineol formulation (G
16) showed a higher promotion effect on the skin of the lower leg of human than the formulation G12 combined with other "promoter". The effect of different receiving phases on the percutaneous penetration of piroxicam is shown in FIG. Regardless of G1 and G16, there was no statistically significant difference in the osmotic effect with or without 30% DMSO. 20% as a single "accelerator"
The effect of adding 20% DMSO to the terpineol G16 formulation and examining the effect on percutaneous penetration into human lower leg skin was examined, and the results are shown in FIG. The permeation effect was slightly inferior to G16 without the addition of 20% DMSO compared to G16 without the addition.

The gel G1 containing no “promoter” was used as a control group, and G8 containing 10% β-myrcene, 10% β-
Mixed formulation of myrcene and 10% terpineol G12, and four formulations of G16 containing 20% terpineol, abdominal skin of nude mouse (I) and abdominal skin of rabbit (I)
I) and in vitro penetration effect on human lower leg skin (III) were compared. The results are shown in FIGS. The cumulative permeation amount per unit area of nude mouse skin left in phosphate buffer at pH 7.4 for 72 hours was 29.5 times, 19.5 times for G1, G8, G12 and G16, respectively, compared to human lower leg skin.
They were 5.9 times, 53 times and 44.4 times. 72 in rabbit skin
The accumulated amount per unit area after 5.5 hours was 5.5 times, 6.2 times, 33.8 times and 47 times that of human skin, respectively. In other words, the abdominal skin of nude mice is 16 times lower than that of human lower leg.
~ 53 times, rabbit abdominal skin 5 times lower than human lower leg skin
This indicates that the penetration amount is ~ 47 times. Figure 2
As shown in Tables 2 to 23 and Table 9, G1 of the control group and
When G16 containing 20% terpineol was left in a 30% DMSO buffer for 72 hours, the cumulative permeation of rabbit skin per unit area was 0.5 times and 14 times that of human skin, respectively.

A control group G1 and a G16 preparation containing 20% terpineol were applied to rabbit abdominal skin by a fully automatic transdermal absorption system (Auto-UV) and a conventional transdermal absorption system for 72 hours.
The permeate accumulation per unit area of time was compared. As shown in FIG. 24, G1 and G16 were 90.5 μg / cm ² and 72 μg / cm ² (80 times) in the fully automatic system, respectively. There was a slight difference in the promoting effect of G16 in the conventional type, but there was no statistically significant difference in G1. When the correlations are compared, as shown in FIGS. 25 to 26, the correlations are very good, and the fully automatic absorption device has specificity.

Each of tenoxicam and isoxicam is represented by C
A permeation test of rabbit abdominal skin was performed as compared with a control group in which MC Na and ethylene glycol were added to a base, and 20% terpineol was added to 30% DMSO buffer. As shown in Table 10, 72 obtained by the fully automatic system were used.
The percutaneous absorption over time was as follows: the cumulative permeation amount of tenoxicam per unit area was 7276.5 μg / cm ² ,
g / cm ² was 86.3 times. Per unit area penetration cumulative amount of isoxicam is 6928.9μg / cm ^2, it was 18.6 times the 372.8 μg / cm ² of the control group. These indicate that the present invention also has a remarkable transdermal absorption promoting effect with other oxicam drugs.

[0018]

[Example 1]

Preparation of piroxicam gel (formulation number G1) 4% w / w piroxicam is added to 20% w / w ethylene glycol and dissolved. Separately, add 2% w / w CMC Na to water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Tables 4 and 5, and FIG.

Example 2 Preparation of piroxicam gel containing 2% glycirizine (Formulation No. G2) 4% w / w piroxicam and 2% w / w glycirizine in 20%
Add and dissolve in w / w ethylene glycol. 2% separately
Add w / w CMC Na to water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Table 4 and FIG.

[Examples 3 to 7] Preparation of piroxicam gel containing 2% of various Chinese herbal medicine accelerators (formulation numbers G5, G7, G9, G20, G21) 2% w / w each in the same manner as in the preparation method of Example 2. Oleanolic acid, betulin, ursolic acid, digitonin, trans-
Take cinnamic acid and prepare a piroxicam gel containing 2% Chinese medicine accelerator. The results of transdermal absorption are shown in Tables 4 and 5, FIG.
This is shown in FIGS.

[Examples 8 to 11] Preparation of piroxicam gel containing 5% of various Chinese herbal medicine accelerators (Formulation Nos. G3, G4, G6, G14) As in the preparation method of Example 2, each of 5% w / w trans -Cinnam aldehyde, (+)-catetin, (1s)-(-)-α
-Take pinene and β-myrcene to prepare a piroxicam gel containing 5% Chinese medicine accelerator. The results of the percutaneous absorption are shown in Tables 4, 5, 5, 3, and 9.

[Examples 12 to 20] Preparation of piroxicam gel containing 10% of various Chinese herbal medicine accelerators (formulation numbers G8, G11, G15, G17, G19, G
26, G28, G29, G30) In the same manner as in the preparation method of Example 2, 10% w / w of β-myrcene, terpineol, ethyl myristate, ergosterol, (+)-limonene, terphenyl, lauryl alcohol, Take cineole and prepare piroxicam gel containing 10% Chinese medicine accelerator. In addition, a piroxicam gel containing 10% Tween 80 is prepared. The results of the percutaneous absorption are shown in Tables 4, 5, 5, 9, 10, and 11.

Examples 21 to 25 Preparation of piroxicam gel containing 15% or more of various Chinese herbal medicine accelerators (Formulation Nos. G10, G13, G16, G31, G3
2) In the same manner as in the preparation method of Example 2, take 15% w / w of β-myrcene, terpineol, or 20% w / w of terpineol, cineole, or 30% w / w of terpineol, and prepare 15% or more of terpineol. A piroxicam gel containing a Chinese medicine accelerator is prepared. The results of transdermal absorption are shown in Tables 4, 5 and 5,
This is shown in FIGS. 10, 12, 14, 15, 16, and 17. FIG.

[Examples 26 to 28] Preparation of piroxicam gel containing two kinds of various herbal medicine accelerators (Formulation Nos. G12, G18, G27) As in the preparation method of Example 3, 10% w / w β- Terpineol in the same amount as myrcene, 10% ethyl myristate and the same amount of terpineol, 15% w / w β-myrcene
A 10% w / w terpineol is mixed to prepare a piroxicam gel containing two Chinese herbal accelerators. The results of the percutaneous absorption are shown in Tables 4, 5 and 5 and 8.

Example 29 Preparation of Tenoxicam Gel 4% w / w tenoxicam is added to 20% w / w ethylene glycol and dissolved. Separately, add 2% w / w CMC Na to water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Table 10 and FIG.

Example 30 Preparation of isoxicam gel 4% w / w isoxicam is added to 20% w / w ethylene glycol and dissolved. Separately, add 2% w / w CMC Na to water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Table 10 and FIG.

Example 31 Preparation of isoxicam gel containing 20% terpineol 4% w / w isoxicam and 20% w / w terpineol were mixed with 20% terpineol.
Add to% w / w ethylene glycol and dissolve. Separately 2
Add% w / w CMC Na to the water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Table 10 and FIG.

Example 32 Preparation of Tenoxicam Gel Containing 20% Terpineol All 4% w / w tenoxicam and 20% w / w terpineol were combined with 20% terpineol.
Add to% w / w ethylene glycol and dissolve. Separately 2
Add% w / w CMC Na to the water and dissolve uniformly. Both are put in a mortar and homogenized, and an appropriate amount of water is added to make 100 ml. The results of transdermal absorption are shown in Table 10 and FIG.

Example 33 Human skin, rabbit skin, and 7-9 week old male ICR nude mouse skin were used as the skin (membrane) material sandwiched between the upper and lower layers of the in vitro percutaneous penetration test apparatus. Secure with fixing clips. Perform a 72-hour penetration test with various transdermal absorbents.At each set time, collect 200 μl of 0.05 M phosphate buffer as a sample solution from the sample outlet, analyze the main component by high-speed chromatography, Calculate the permeation amount of the drug from, and judge the degree of release of various preparations. The results of transdermal absorption are shown in Table 8, FIG.
23 to FIG.

[0030]

[Table 1]

[0031]

[Table 2]

[0032]

[Table 3]

[0033]

[Table 4]

[0034]

[Table 5]

[0035]

[Table 6]

[0036]

[Table 7]

[0037]

[Table 8]

[0038]

[Table 9]

[0039]

[Table 10]

[0040]

According to the present invention, in a transdermal drug delivery system containing an anti-inflammatory agent oxicam as a main drug, a specific Chinese medicine component , that is, oleanolic acid, glycine is used.
Silidine, β-myrcene, trans-cinnam alde
There are hide, cineole, betulin, pinene and digitonin
Or at least one of the herbal components of ursolic acid
By adding it as an accelerator, the anti-inflammatory agent oxicam
High percutaneous absorption-promoting effect than alone Ru obtained. Further, the percutaneous absorption preparation of the present invention can be applied to dosage forms such as ointments, suspensions, gels, solutions, sprays and patches, and is clinically convenient.

[Brief description of the drawings]

FIG. 1 is an explanatory diagram of an anti-inflammatory and antipyretic analgesic having an oxicam structure.

FIG. 2 is a configuration diagram of an in vitro percutaneous penetration test apparatus.

FIG. 3 is a graph showing the percutaneous absorption (accumulated permeation amount) of the Chinese medicine component “promoter” in the abdominal skin of nude mice (G6, G7, G4 in the figures including the following figures)
・ ・ See Tables 1 and 2).

FIG. 4 is a graph showing the percutaneous absorption of a Chinese medicine component “promoter” in abdominal skin of a nude mouse.

FIG. 5 is a graph showing the percutaneous absorption of a Chinese medicine component “promoter” in abdominal skin of a nude mouse.

FIG. 6 is a graph showing the percutaneous absorption in the abdominal skin of nude mice by different concentrations of the Chinese medicine component “promoter”.

FIG. 7 is a graph showing the percutaneous absorption in the abdominal skin of nude mice by different concentrations of the Chinese medicine component “promoter”.

FIG. 8 is a graph showing the percutaneous absorption in the abdominal skin of nude mice by a single or a mixture of two kinds of Chinese medicine components “promoter”.

FIG. 9 is a graph showing the percutaneous absorption of a Chinese medicine component “promoter” in rabbit abdominal skin.

FIG. 10 is a graph showing the percutaneous absorption of the Chinese medicine component “promoter” in abdominal skin of nude mice.

FIG. 11 is a graph showing the percutaneous absorption of a Chinese medicine component “promoter” in abdominal skin of a nude mouse.

FIG. 12 is a graph showing the percutaneous absorption of rabbit herb abdominal skin by different concentrations of the Chinese medicine component “promoter”.

FIG. 13 is a graph showing percutaneous absorption in rabbit abdominal skin by different concentrations of piroxicam gel.

FIG. 14 is a graph showing percutaneous absorption in rabbit abdominal skin by different receiving buffer solutions with a 20% terpineol formulation.

FIG. 15 is a graph showing the percutaneous absorption in human lower limb skin by different concentrations of a Chinese herbal medicine ingredient “promoter”.

FIG. 16 is a graph showing percutaneous absorption in human lower limb skin by different receiving buffer solutions with a 20% terpineol formulation.

FIG. 17 is a graph showing transdermal absorption of terpineol and DMSO in human lower limb skin.

FIG. 18. Percutaneous absorption of four formulations in different skins
It is a graph shown about (G1).

FIG. 19: Transdermal absorption of the four formulations in different skins
(G8: 10% β-myrcene).

FIG. 20: Percutaneous absorption of four formulations in different skins
(G12: 10% β-myrcene + 10% terpineol).

FIG. 21. Percutaneous absorption of the four formulations in different skins.
It is a graph shown about (G16: 20% terpineol).

FIG. 22. Percutaneous absorption of two formulations in different skins
(G16: 20% terpineol).

FIG. 23. Percutaneous absorption of two formulations in different skins
It is a graph shown about (G1).

FIG. 24 is a graph showing the amount of permeation accumulated by a fully automatic percutaneous absorption device and a conventional percutaneous absorption device.

FIG. 25 is a graph showing the percutaneous absorption of different anti-inflammatory agents in rabbit abdominal skin.

FIG. 26 is a graph showing the percutaneous absorption of different anti-inflammatory agents in rabbit abdominal skin.

FIG. 27: Fully automatic transdermal absorption analyzer analysis and HP of oxicam
It is a graph shown about the relevance of LC analysis.

FIG. 28: Fully automatic percutaneous absorption analyzer analysis and HP of oxicam
It is a graph shown about the relevance of LC analysis.

FIG. 29: Fully automatic percutaneous absorption analyzer analysis and HP of oxicam
It is a graph shown about the relevance of LC analysis.

Continued on the front page (51) Int.Cl. ⁷ Identification code FI A61K 47/06 A61K 47/06 47/22 47/22 47/28 47/28 A61P 29/00 A61P 29/00 (56) References JP JP-A-3-109327 (JP, A) JP-A-2-138220 (JP, A) JP-A-6-279289 (JP, A) JP-A-4-305523 (JP, A) JP-A-6-24965 (JP) JP-A-49-35411 (JP, B1) JP-T-Hei 8-500365 (JP, A) International Publication No. 91/5529 (WO, A1) Chem. Ab. Abstract No. 124: 211820 (STP Pharma Sci., Vol. 5, No. 6, (1995), p. 461-7) (58) Fields investigated (Int. Cl. ⁷ , DB name) ) A61K 31/5415 A61K 9/06 A61K 9/08 A61K 9/107 A61K 9/70 A61K 47/06 A61K 47/22 A61K 47/28 A61P 29/00 CA (STN)

Claims (4)

(57) [Claims] 1. An anti-inflammatory antipyretic oxicam having a concentration of 0.1 to 50%.
Painkillers, Oleanolic acid, glycylidine, β-myrcene, trans
-Cinnamaldehyde, cineole, betulin, pinet
Or at least one of digitonin or ursolic acid
0.1-70% accelerator consisting of different Chinese herbal ingredients, If necessary, a transdermal absorption excipient, Percutaneous absorption of oxicam
Yield formulation. 2. The oxicam anti-inflammatory and antipyretic analgesic according to claim 1.
Soxicam, Sudoxicam, Synoxicam, Tenoxica
Romoxicam or piroxicam
A percutaneous absorption preparation of oxicam according to claim 1, which is characterized by: 3. The transdermal excipient according to claim 1, wherein the excipient is 0.01 to 99.9.
5% range, ethylene glycol or carboxy
Characterized as sodium methyl cellulose
The percutaneous absorption preparation of oxicam according to claim 1. 4. Ointments, suspensions, gels, solutions, sprays
Or in the form of a patch.
Item 10. A transdermal absorption preparation of oxicam according to Item 1.