JPH0768128B2 - Antipruritic, antipruritic, anti-inflammatory agent - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an antipruritic, antipruritic and antiphlogistic agent containing a metal phthalocyanine derivative as an effective main component.

[0002]

BACKGROUND OF THE INVENTION Patients with fractures are forced to cast for long periods of time to treat them. While I am wearing a plaster cast, I cannot take a bath or wipe the affected area. This is especially noticeable in the summer when sweating is intense. In addition to water, the components of sweat include lactic acid,
Urea, salt, ammonia, proteins, fats, cholesterol, glycerides, waxes, etc., which are the origin of bacteria that proliferate and ferment to give off a bad odor, which irritates the skin and causes itching.

Conventionally, in the books, it is necessary to take measures against itching by casting.
Clean the skin by wiping the body, insert a thin stick or grandson's hand into the cast and scratch directly, hit the affected area directly from the top of the cast, cool it, wipe the area outside the cast with alcohol. , Try to dry by blowing the sun or a fan, try to change your mood by immersing yourself in video games and work, etc.If the above methods do not reduce your itch, antihistamines and tranquilizers are supposed to be given. I have to question the positive effect.

To prevent the bad odor, try to eliminate the bad odor with a spray type fragrance or other perfume, or wipe the peripheries of the wounded area as often as possible and use a hygroscopic powder. I was just doing sweat removal. For such malodor, the deodorant containing a metal phthalocyanine derivative as a main component disclosed in JP-A-56-63355 is effective.

[0005]

[Problems to be Solved by the Invention] There has been no effective countermeasure against itching. Among patients with fractures, those who have had some pruritic skin disease as a previous disease often get old itching of the skin when wearing a cast for the treatment of bone fractures, which worsens and causes inflammation in many cases.

[0006] Further, in the treatment after removing the cast, the treatment of sprains, bruises and the like, when continuing the compress therapy, there is a problem of skin reaction. When the reaction is high, a vicious cycle of erythema, pruritus, scratching, rash, and increase in pruritus comes to occur, and there are cases where the continuation of compress therapy must be stopped.

[0007] The present invention improves the above-mentioned conventional treatments and provides an extremely effective antipruritic, antipruritic and anti-inflammatory agent.

[0008]

The inventor of the present invention uses a deodorant containing a metal phthalocyanine derivative as a main component disclosed in JP-A-56-63355 to eliminate a bad odor caused by a cast. While continuing the research described above, it was found that the metal phthalocyanine derivative is effective against itch, and the present invention has been completed.

That is, the antipruritic, antipruritic and anti-inflammatory agents of the present invention are:
The following [I] expression

[0010]

[Chemical 1]

An active ingredient containing a metal phthalocyanine derivative represented by However, n1 to n4 in the formula [I] are the same
2 and M is a metal selected from Fe, Co, Mn, Ti, V, Ni, Cu, Zn, Mo, W and Os. The substituents R1 to R4 are preferably carboxyl groups.
Good

A metal phthalocyanine derivative in which the substituents R1 to R4 in the formula [I] are carboxyl groups and n1 to n4 are 1.
That is, the following [II] formula

[0013]

[Chemical 2]

The metal phthalocyanine tetracarboxylic acid represented by is particularly effective.

In the formula [I], a metal phthalocyanine derivative in which R1 to R4 are carboxyl groups and n1 to n4 are 2, that is, the following formula [III]

[0016]

[Chemical 3]

The metal phthalocyanine octacarboxylic acid represented by is also particularly effective.

The central metal M in the formulas [I] to [III] is defined as described above, but a high spin type of Fe, Co or Mn is particularly preferable.

Iron phthalocyanine tetracarboxylic acid, which is a particularly preferred example, can be obtained as follows. Trimellitic anhydride, urea, ammonium molybdate, and ferric chloride anhydride are added to nitrobenzene, and the mixture is stirred and heated to reflux to obtain a precipitate. It is obtained by decomposing and then acidifying by adding an acid. Cobalt phthalocyanine octacarboxylic acid, which is also a preferred example, is pyromellitic acid anhydride in place of trimellitic acid anhydride, which is a raw material of the iron phthalocyanine tetracarboxylic acid, and ferric chloride in place of ferric chloride. It can be manufactured using the same method. Details of the method for producing the metal phthalocyanine derivative are disclosed in several documents including the above-mentioned JP-A-56-63355.

The metal phthalocyanine derivative is carried on a fiber material such as gauze, bandage, underwear, woven fabric including supporter, non-woven fabric, knitted fabric, papers in an amount of about 0.001 to 5% by weight, and the gauze and the like. It becomes effective by applying to the affected area. If the supported amount is 0.001 % by weight or less, the drug effect is insufficient, and it is difficult to support more than 5% by weight on the fiber material. Fiber materials include, for example, cellulosic fibers (cotton, hemp, rayon, etc.), protein fibers (wool, silk, etc.), polyamide fibers, polyester fibers, polyacrylic fibers, poval fibers, polyvinyl chloride fibers, Any natural fiber such as polyvinylidene chloride fiber, polyolefin fiber, polyurethane fiber, regenerated fiber, semi-synthetic fiber, or synthetic fiber is used. In addition to such organic fibers, inorganic fibers such as asbestos fibers, glass fibers, ceramic fibers, metal fibers and carbon fibers may be used. Among them, cellulosic fibers, especially cotton,
Since it has good water absorbency, it absorbs perspiration from the affected area well and brings about a synergistic effect in suppressing itch, which is particularly preferable.

In order to support the metal phthalocyanine derivative, especially the metal phthalocyanine polycarboxylic acid, on the fiber, it is preferable that the fiber is previously treated with a quaternary ammonium salt compound to be cationized. The cationized fiber is immersed in an aqueous solution of a metal phthalocyanine polycarboxylic acid and then dried, so that the drug active ingredient is supported on the fiber.

In order to obtain a poultice having antipruritic, antipruritic and antiphlogistic effects, about 0.0000001 to 10% by weight of a metal phthalocyanine derivative is kneaded into kaolinite or swelling soil such as montmorillonite (bentonite) which is a poultice base. Kneading amount
If it is less than 0.0000001% by weight, the drug effect will be insufficient, and if it is kneaded in excess of about 10% by weight, the drug effect will be saturated and it will be economically unprofitable. In particular, since montmorillonite has a large amount of clathrate space itself, it can contain a sufficient amount of water and a sufficient amount of drug as a poultice for a long period of time, and because it has a high heat and toxin adsorption property, it has a good medicinal effect and lasts a long time. .

In order to obtain a poultice having antipruritic, antipruritic and antiphlogistic effects, fibers carrying a metal phthalocyanine derivative are finely cut into powder and kneaded into a poultice base or kneaded into a commercially available poultice. It can also be used in a complicated manner.

It is also effective to mix the metal phthalocyanine derivative in an ointment base such as glycerin or petrolatum and apply the mixture to the affected area. In addition, the metal phthalocyanine derivative may be mixed alone or together with an extender in the adhesive component of the adhesive bandage, and the adhesive may be applied to the affected area. For example, it is also possible to carry a metal phthalocyanine derivative on an inorganic or organic substance such as various kinds of ceramic powders such as alumina and cristobalite, activated carbon, silica gel, zeolite, starch and gelatin, and then use the same as above.

[0025]

[Function] The antipruritic, antipruritic, and antiphlogistics containing a metal phthalocyanine derivative as the main component have been confirmed to be effective through clinical experiments, and their actions as drugs have not necessarily been theoretically elucidated. However, it is estimated that it is as follows.

There are various causes of itch, and one of the causes may be histamine or a histamine-like substance produced in the body. Histamine contains ethylamino and imidazole groups and is zwitterionic. It is known that this imidazole group is coordinated with the central metal of the metalloporphyrin having a structure similar to that of the metal phthalocyanine. The imidazole group in histamine is strongly coordinated with the central metal M of the metal phthalocyanine derivative, and histamine is adsorbed and the concentration thereof is reduced. As a result, the concentration of histamine is suppressed below the threshold value at which itching is felt, and itching is thought to be no longer felt.

This antipruritic, antipruritic and anti-inflammatory agent works most effectively when the drug components come into direct contact with the affected area, but, surprisingly, they are also effective against distant affected areas where the drug components do not come into direct contact. I knew it was. When histamine is adsorbed on the metal phthalocyanine derivative and the concentration decreases, the concentration gradient with histamine in other parts of the body becomes remarkable, and the histamine in other parts also contacts the low concentration part, that is, the metal phthalocyanine derivative. Focus on the part. Histamine concentrated from other parts of the body is also adsorbed by the metal phthalocyanine derivative. Therefore, only when the metal phthalocyanine derivative is in contact with the skin, the concentration of histamine in the whole body is lowered and the allergic symptoms caused by histamine are alleviated.

[0028]

【Example】

<< Example of use of bandage treated with antipruritic, antipruritic, and antiphlogistic agent >> An example of using the antipruritic, antipruritic, and antiphlogistic agent of the present invention on a tubular knitted bandage (hereinafter referred to as "stockinette") Will be described in detail.

A stockinette made of 100% cotton yarn is treated with a cationic surfactant, dipped in a 3% aqueous solution of iron phthalocyanine tetracarboxylic acid and then dried in the shade to give a stockinette with antipruritic, antipruritic and anti-inflammatory agents. Obtained.

The anti-pruritic, anti-pruritic and anti-inflammatory drug stockinets were used as lower rolls of casts in 108 fracture patients, and the conditions of itching, odor, sweat and other side effects were observed. Of the 108 fracture patients, 61 were those with a history of pruritic skin diseases and 47 were those without a history of pruritic skin diseases. Pruritus in the following Tables 1 to 4,
The history of skin diseases of 108 bone fracture patients using antipruritic and anti-inflammatory stockinette is shown by condition. Table 1 shows the number of bone fracture sites for each history of skin diseases of bone fracture patients. In the parentheses, the number (36 cases in total) when the cast was used as an under-roll of the cast after surgery was performed for the treatment of bone fractures is shown. Table 2 shows the number of people in the age distribution for each history of skin diseases of fracture patients. Table 3 shows the number of people who wear plaster casts for each history of skin diseases of fracture patients. Table 4 shows the number of people in the cast wearing season for each history of skin diseases of fracture patients.

[0031]

[Table 1]

[0032]

[Table 2]

[0033]

[Table 3]

[0034]

[Table 4]

The distribution of patients and the therapeutic effects when using anti-pruritic, antipruritic, and stockinette with an anti-inflammatory agent under the conditions are as follows.

Nine out of 61 persons, who had any history of itchy skin disease, complained of itching or discomfort on the night of wearing the cast. But from the next day,
All nine patients were able to sleep well without itching or discomfort. The remaining 52 patients out of 61
There was no itch from the day I put it all on.

In the above examples, the effect on itching was shown, but the antipruritic, antipruritic, and anti-inflammatory agent Stockinette had a remarkable effect on the odor, and the pleasing feeling of the cast was good, and the evaluation is described below. To do.

Two doctors and nurses directly smelled and evaluated the odor. After wrapping a plaster with antipruritic, antipruritic, and anti-inflammatory agent, the cast was applied once a week to once every two weeks, and to the inpatient every day. Of the 108 patients, the sweet and sour odor of sweat was slightly observed in 3 patients treated in the summer. The other 105 had little odor. All three patients who had an odor stated themselves as having hyperhidrosis. It was said that all the patients felt that the cast was always dry and refreshing.

No findings that could be considered as side effects were observed in all 108 patients.

Next, the main ones from the individual concrete clinical cases will be introduced.

Case 1: Woman with osteogenesis deficiency Atopic dermatitis has been a specialist since about 2 years old,
On the other hand, five fractures have been repeated in the past, and each time, the cast is treated. The first fracture was an upper right humeral fracture at the age of six. The second time was 8 years old and fractured the left humerus. The third time was 12 years old and fractured the left femur. The fourth time was 13 years old and had a fracture of the left femur.

At the first and second times, a cast was wrapped and the treatment was carried out as an outpatient. At home, she couldn't sleep at night due to itching, and she couldn't sleep at night.
In the 3rd and 4th sessions, after admission and traction therapy, a cast was wound using stockinette made of cotton thread without antipruritic, antipruritic, and anti-inflammatory agents. According to his mother, he was able to sleep deeply to the third and fourth times and was comfortable in the hospital. By the way, the first and second injuries were in autumn and fall, and the third and fourth injuries were in winter.

The fifth time, at the age of 15, fractured the left lower leg bone in the summer. He was admitted to the hospital for traction therapy and put on a plaster cast with antipruritic, antipruritic and anti-inflammatory stockinette. He was discharged from the hospital about two weeks after the injury. About 2 to remove the cast
He did not complain of itching for months. A large amount of exfoliation of old skin was observed when the cast was removed, but there was no bad odor.

Case 2: 12-year-old female A left femur was fractured in a traffic accident. During treatment, it was pulled by a steel wire. After about 4 weeks, the cast was fixed from the waist to the legs. For fixing with a plaster cast, antipruritic, antipruritic and stockinette with anti-inflammatory agent were wound underneath.

In the case of this patient, an abnormality was observed on the skin before using the cast. There was a rash on the whole body, and the skin on the whole body tended to be dry. Eczema was seen on the dents on both elbows and on the back of the knee. My mother said, "Since I was a baby, I had rough skin. I had been complaining about itching around my butt since last year, so when I visited a dermatologist, I felt allergic,
The patient was diagnosed with so-called atopic dermatitis and was given a topical steroid hormone preparation. After that, the symptoms did not improve, but from this year the rash spread to the lower body and became a little worse. Recently, in addition to external preparations, two kinds of internal medicines have come to be used in combination. He said.

When it was fixed with a cast using an antipruritic, antipruritic, and stockinette with an anti-inflammatory agent, itching disappeared from that night, and no pruritus was reported even at a site other than the part where the cast was fixed. There was no smell in the cast. The cast fixed period was about 2.5 months. A large amount of exfoliation was observed when the cast was removed, but the symptoms of the skin disease were almost improved.

Case 3: 70-year-old male, fracture of the upper left lower leg. Three years ago, after undergoing abdominal surgery twice, a generalized rash appeared after a while. The skin of the whole body became dry, and chronic eczema-like changes were observed on the extensor side of the lower leg and the vulva, and rash and purulence due to partial scratching were observed. Dermatologists used atopic corticosteroids, internal medicines, non-steroidal external medicines, antihistamines, antibiotics, etc. even if they had atopic skin.

This time, the upper part of the left lower leg was fractured. When he told him that he would use a cast to treat a fracture, he refused, "I couldn't sleep because of itching until now, so I might die from the age of the cast if I roll it up." However, with the doctor's strong recommendation, the above antipruritic, antipruritic, and stockinette with anti-inflammatory agent were wrapped from the upper thigh to the toes and a cast was put on. According to him, he felt itchy at night with antipruritic, antipruritic and stockinette with anti-inflammatory agent, but he did not feel itching itself. Itching has completely disappeared from the next day, and he says that he continues to spend his days comfortably.

Case 4: 22-year-old male open fracture of lower leg bone Injured in August, fixed with a cast splint immediately after visiting the hospital, and subjected to bone joint surgery 7 days after the injury. When the cast splint that had been fixed at the time of osteosynthesis was removed, the cast splint had a bad odor due to contamination with blood and secretions of dermatitis. Patients complained that some nights itched and couldn't sleep well.

After the joining operation, an antipruritic, antipruritic, and stockinette with anti-inflammatory agent was wound under and fixed with a cast. The next day, blood from the surgical wound was leaking onto the cast. The wound was opened two weeks later. Not only the surgical wound but also the surrounding dermatitis was healed. Gauze, antipruritic, antipruritic, anti-inflammatory stockinette,
Although the cast had bloody coloring, it was dry and clean without bad odor. The cast was removed after about 3 months. At that time, a large amount of exfoliation of the skin was observed. Itching did not complain all the time.

<< Example of use of poultice containing antipruritic, antipruritic and antiphlogistic >> Examples of using the antipruritic, antipruritic and antiphlogistic of the present invention mixed with poultice will be described in detail below. .

100 g of a commercially available poultice (in 100 g of ingredients, Japanese Kaolin 37.30 g, dl camphor 0.24 g, peppermint oil 0.05 g, thymol 0.01 g, methyl salicylate 0.20 g, diphenhydramine 20.01 g, propylene glycol 6.24 g, residual water content )
Then, 30 g of a finely divided powder of rayon fiber carrying 1% by weight of iron phthalocyanine tetracarboxylic acid is mixed and stirred to prepare a poultice sample for embedding. The rayon fiber carrying iron phthalocyanine tetracarboxylic acid is obtained by immersing rayon staple in an aqueous solution of iron phthalocyanine tetracarboxylic acid and then drying.

The obtained sample poultice was applied to the treatment of lumbar bruises, thigh bruises, thigh bruises, knee sprains, ankle sprains, hand sprains, periarthritis of the shoulders, and rheumatic diseases. Used for patients in need of therapy. A total of 20 patients were selected, including 10 patients who had pruritic skin disease as a preexisting disease and were prone to rash, and 10 general patients who did not have such a preexisting disease.

A poultice is prepared by applying a sample poultice of the above-mentioned formulation to gauze or flannel to a thickness of about 0.5 cm and applying it to the affected area. The frequency of replacement of the sample poultice was determined according to the written instructions for the commercial poultice.

As a result, no skin reaction was observed in any of the patients during the treatment period, and none of them complained of itching. Therefore, there was no pain caused by the compress treatment and he could concentrate on the original wound treatment, and all of them recovered smoothly. Usually, when using a commercially available poultice, more than half of the patients complain of itching, and in severe cases, redness,
Although there are some people who develop pus and a feeling of heat and discontinue the compress treatment, significant improvements have been made to such symptoms.

Further, this sample poultice was burned once (2
Name), insect puncture wounds (5 people), dermatitis after fixing the adhesive plaster (5
First name). The wounds and inflammation also showed good recovery.

No findings that could be considered side effects were observed in all 32 patients.

[0058]

As described above in detail, the antipruritic, antipruritic and anti-inflammatory agents of the present invention can effectively relieve itch by including a metal phthalocyanine derivative as an active ingredient. Further, it also has a deodorizing effect which is a property of conventionally known metal phthalocyanine derivatives. It is very preferable when the cast is used for a long period of time such as treatment of bone fracture or ligament injury.

Claims (4)

[Claims] 1. A compound represented by the general formula [I]: (In the formula [I], R1 to R4 are carboxyl groups, and n1 to n4 are the same.
1 or 2, M is a metal phthalocyanine derivative represented by Fe, Co, Mn, Ti, V, Ni, Cu, Zn, Mo, W, and Os)) as an active ingredient. Pruritus, antipruritic, anti-inflammatory agent. 2. The antipruritic, antipruritic, and antiphlogistic agent according to claim 1, wherein the active ingredient contains a metal phthalocyanine derivative in which M is Fe, Co or Mn in the formula [I]. 3. A fiber cloth with antipruritic, antipruritic, and antiphlogistic agent, which comprises a metal phthalocyanine derivative represented by the formula [I] as an active ingredient carried on fibers. 4. Antipruritic, antipruritic, characterized in that the metal phthalocyanine derivative represented by the formula [I] is mixed.
Anti-inflammatory compress.