JPH0259519A - Remedy for skin inflammation - Google Patents

Abstract

PURPOSE:To obtain a remedy for skin inflammation having slight irritation and excellent stability comprising ubidecarenone as an active ingredient. CONSTITUTION:The aimed substance is obtained by blending 0.05-5%, preferably 0.1-2% ubidecarenone as an active ingredient with glycerin, squalane, cetyl alcohol, egg yolk phospholipid, glyceryl fatty acid ester, etc., and pharmaceutically manufacturing by a conventional procedure for skin administration. Ubidecarenone is extracted from mitochondria of bovine cardiac muscle, has 48-52 deg.C melting point, is yellow-orange crystalline powder, fat-soluble and hardly soluble in water and methanol. The aimed substance can be processed into a form such as into cream, milky lotion or ointment. The aimed substance has excellent effects on dermatitis, especially on acute inflammation.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a therapeutic agent for skin inflammation containing ubidecarenone as an active ingredient.

That is, the present invention is an invention for the medical use of ubidecarenone, and is an invention used for the treatment of dermatitis in the medical field.

The present inventor attempted various studies with the aim of treating dermatitis by administering drugs. As a result, it was discovered that remarkable healing results can be obtained by applying ubidecarenone directly to the inflamed site, and the present invention has been completed.

That is, the present inventor has cited the following documents 2), 3), 4), 5
), 6), we have previously attempted to use ubidecarenone for the treatment of radiation dermatitis or radiation ulcers, pressure ulcers, burns, and wounds, and the results showed that it was effective. However, since the causes and conditions of dermatitis are different from radiation dermatitis, radiation ulcers, bedsores, burns, and wounds, it is natural that ubidecarenone would be equally effective against dermatitis. I couldn't have predicted it. However, surprisingly, remarkable hardening results were confirmed as described above, and the present invention was completed.

Therefore, the purpose of the present invention is to treat dermatitis, and to achieve this purpose, the present invention provides a therapeutic agent characterized in that ubidecarenone is administered to the site of inflammation.

1) Okuyama, Nis, And Misina, Etsuchi: Brincivia Saibu Cancer Tellabi, ■, Rescue Saibradiation Damage, Saie, Revo Lisa Insci, Tohoku Universal, -C29: 1.1
982゜(Qkuyaa+a, S, and 1Ji
Shina, H.: Princi-pia of
cancer therapy, 1. Re5c
ue offradiation dao+age, S
ci, Rep, Res, In5t.

Tohoku Univ, -C29: 1. 1
982.12) Okuyama, Nis, and Mishina, Etsuchi: Brinsibia Saibu Cancer Terrabee, ■,
Application Saibu Ubiquinone Oinment for Intractable Radiation Arthur: Unexpanded Cytochrome Sea Effect Saie, Revo, Lisa, Insuti, Tohoku Universal, -(: 30: 36.1983゜fo
kuyama, S. and Mishina, H.
, : Pr1nci-pia of cancer t
therapy, Vl, Applicationno
f ubiquinone ointment
for 1ntractable radiation
ulcers: An expanded cyto
chromec effect Sci, Rep,
Res, In5t, TohokuUniv,
-C30: 36, 1983.13) JP-A-6O-1
00517 4) JP-A No. 61-2) 002) 1 The present invention will be described in detail below. Since ancient times, the four signs of inflammation are fi1 redness, (2) swelling, and (3) pain f4N!
! This is known to cause a decline in the patient's ability, and is used as a guideline for medical treatment as a measure of treatment effectiveness.

In the present invention, it was used to evaluate the clinical efficacy of ubidecarenone ointment.

Highly specific acute inflammation refers to those in which, in addition to these four symptoms, tissue necrosis and seborrhea formation are observed.

The dermatitis of the present invention is interpreted in a broad sense, and the causes include both extrinsic and endogenous causes.

For example, extrinsic dermatitis includes contact dermatitis, commonly known as rash, insect bites, and diaper rash.

On the other hand, endogenous causes include seborrheic eczema caused by allergies, atopic dermatitis, and eczema caused by drugs, that is, drug eczema. Although the pathophysiology of dermatitis changes over time with local changes and systemic changes, the present invention is not particularly limited by these changes.

Next, ubidecarenone is ubiquinone or supplementary oxygen Q.
,. Also known as ubidecarenone, which has traditionally been used medicinally as a therapeutic agent for congestive heart failure, may be used in the present invention. Ubidecarenone is extracted from the mitochondria of bovine myocardium and is known to be involved in the electron transport chain. It is being Therefore, ubidecarenone improves oxygen utilization in the myocardium even when the myocardium is in an ischemic state.

It makes it possible to maintain a high ATP production function.

As a result, it is known that ubidecarenone reduces the damage caused to ischemic myocardial tissue and improves the decline in cardiac systolic function.

However, the fact that dermatitis can be effectively cured by ubidecarenone administered through the skin was previously unknown, and was revealed for the first time by the present inventor.

Ubidecarenone is a yellow to orange crystalline powder with a melting point of 48 to 52°C, and is fat-soluble. Almost insoluble in water and methanol. That's it.

Subacute toxicity to male and female Wistar rats 40.200 and 1,000
0 mg/kg/day for 5 weeks and 60 and 6 days for rabbits of both sexes.
00 mg/kg/day was orally administered continuously for 23 days.

In both rats and rabbits, no differences were observed from the control group in general conditions, blood and urine tests, and morphological observations (macroscopically and histologically).

The present invention is characterized in that ubidecarenone is administered to a site where dermatitis as defined above has developed.

Therefore, when administering ubidecarenone directly to the skin, it is preferable to administer it as a preparation suitable for skin application.Also, it is preferable to administer ubidecarenone in combination with other drugs such as cytochrome C, urokinase, etc. However, the present invention is not limited by these combined administrations.

In addition, the amount of ubidecarenone in the therapeutic agent of the present invention is 0.
．． 05 to 5.0% is recommended, more preferably 0°1
An appropriate amount of the therapeutic agent may be applied depending on the size and progress of the dermatitis, preferably 2.0%.

Ubidecarenone has good stability when administered to the skin and is less irritating to the skin. For example, skin - next! 'II f
fi Note, cumulative irritation, eyelid irritation, phototoxicity, sensitization,
Table 1 shows the photosensitivity and batch test results.

In order to make a preparation suitable for dermal administration, it is necessary to select and incorporate suitable ingredients for the preparation with less irritation as ingredients other than ubidecarenone.9 For example, glycerin, squalane, cetyl alcohol, egg yolk phospholipid, glyceryl fatty acid ester. etc., and prepare a preparation for skin administration by a conventional method.

The present invention will be explained in more detail with reference to two examples below.

Example 1 Stearyl alcohol 12.0 wt% Squalane 6.0 Isopropyl myristate 4.0 Ubidecarenone stearate Propylene Glyethyl paraben Butyl paraben Add purified water Total amount 100.0 The above ingredients were mixed in a conventional manner until homogeneous. Tonanashi 1 was used as the therapeutic agent of the present invention.

Example 2 Squalane 15.0 wt% Octyldodecyl myristate 5.0 Hydrogenated soybean oil
5.0 Glyceryl monostearate
1.5 Stearic acid 2.0 Ubidecarenone 1.0 Partially hydrogenated egg yolk phospholipid 1.0 Glycerin
5.0 Ethylparaben
0.3 Antioxidant An appropriate amount of purified water was added, and the total amount was 100.0. The above prescription ingredients were mixed in a conventional manner to obtain a homogeneous norm, which was used as the therapeutic agent of the present invention.

Example 3 Squalane 3. Owt% Octyldodecyl myristate 2.0 Stearic acid
1.2 Glyceryl monostearate
1.0 Tsuru to tan monopalmitate 0.5 Cetyl alcohol 20.5 Cetyl alcohol monopalmitate 0.5 Methyl paraben 0.2 Propylene glycol 5.0 Xanthan gum
0.05 Ubidecarenone 0.
3. Suitable for fragrance] Purified water Total amount: 100.0 The above prescription ingredients were mixed in a conventional manner to form a homogeneous emulsion, which was used as the therapeutic agent of the present invention.

Example 4 Partially hydrogenated egg yolk phospholipid 0.11% ubidecarene! Macrogol 400 4.0 Ethyl Alcohol 8, Ovol, % Propylene Glycol? , 0 ethylparaben 0.1 fragrance
Appropriate amount of antioxidant Add appropriate amount of purified water, total volume 1009 mouths v011% All of the above prescription ingredients except purified water are uniformly dissolved by heating, kept at about 60'C, and poured into purified water preheated to the same temperature. The mixture was added under stirring, mixed uniformly, and cooled to room temperature to produce a ubidecarenone-containing lotion, which was used as the therapeutic agent of the present invention.

Example 5 Solid sweat ε paraffin microcrystalline paraffin cetyl alcohol stearate aluminum ubidecarenone lO liquid paraffin 25.0 Add white petrolatum
Total amount: 100.0 The above prescription ingredients were mixed in a conventional manner to form a homogeneous ointment, which was used as a therapeutic agent of the present invention.

A detailed illustration of the invention is provided by the case report described below.

As the therapeutic agent of the present invention, a woody ointment containing 0.5% of ubidecarenone was used. For treatment, the inflamed area was cleaned and disinfected with Hibitane solution, and then the same ointment was applied externally.

Case 1: A 6-month-old female patient developed diaper rash and acute dermatitis in the perineal area due to diaper rash and acute diarrhea.

After cleaning the affected area, ubidecarenone ointment therapy was started.

The redness and swelling quickly disappeared.

Case 2: A 53-year-old woman was treated for acute contact grade F87 malignant lymphoma. During the treatment of malignant lymphoma, she experienced left-sided chest pain during intravenous injection therapy of an anti-malignant tumor drug, and a poultice was applied to the patient. Several hours later, local heat sensation and pain worsened, and redness, swelling, etc. were observed. Blisters formed after three days. For the pain, anti-inflammatory analgesics were administered, but no analgesic effect was obtained.Acute contact dermatitis was diagnosed, and ubidecarenone ointment therapy was performed, and the severe pain disappeared after 6 applications. In addition, a rapid therapeutic effect on redness, swelling, blisters, etc. was observed.

In this case, a similar left chest syndrome occurred two months ago, and no skin injury was observed even after administering a poultice. h
istamine sensitizing activity
ity).

Case 3: A 51-year-old male with seborrheic eczema. Ubidecarenone therapy was started for seborrheic eczema with redness, excretion, and itching on the back of the left ear. Two days later, the redness, acne, and itching diminished.

Clinically, acute inflammation has four symptoms: redness, local heat, swelling, and pain.6 Histologically, epithelial cell damage, vascular damage, and interstitial damage occur; However, it has been considered difficult to treat all of them. However, ubidecarenone ointment has such potential.
The treatment of acute dermatitis is an easy-to-understand model. That is, ubidecarenone applied topically penetrates the skin well and reaches target cells in the skin and subcutaneous tissue.
Restores the electron transport chain in damaged mitochondria.

As a result, pain is alleviated and disappears. When the same thing happens with vascular endothelial cells, tissue fluid 1 notification decreases and swelling also decreases, making it a worthy treatment for interstitial cells. Clinically, it also means bleb formation, disruption of subcutaneous edema formation, and absorption. The activation of skin cells brings about the restoration of normal skin's urgor and also promotes the regeneration of epithelial cells. Ointment is considered to be one of the innovative drugs that can exert a fairly comprehensive therapeutic effect on dermatitis in general. Possible dosage forms include ointments, lotions, compresses, and sprays. Since no side effects such as hypersensitivity or new contact dermatitis were observed when applied externally, its use not only as a pharmaceutical but also as a quasi-drug is considered realistic.

Patent applicant: Eisai Co., Ltd.

Claims (2)

[Claims] (1) A therapeutic agent for skin inflammation containing ubidecarenone as an active ingredient. (2) The therapeutic agent for skin inflammation according to claim 1, wherein the skin inflammation is acute skin inflammation.