JPH01319427A - Superoxide dismutase-containing pharmaceutical composition for local administration - Google Patents

Abstract

PURPOSE:To obtain a pharmaceutical composition for local administration, containing superoxide dismutase and hyaluronic acid or a salt thereof, effective against dermatosis and excellent in humectant properties and permeability to the skin. CONSTITUTION:A composition containing superoxide dismutase (hereinafter abbreviated to SOD) and hyaluronic acid or a salt thereof. Human SOD or SOD obtained from animals (e.g., cattle) may be used as the SOD. The above- mentioned composition contains the SOD and the hyaluronic acid or salt thereof as active ingredients aid prepared in a dosage form for local administration, e.g., ointment, gel, lotion or cream. The content of the SOD is 0.001-1g, preferably 0.005-0.5g, more preferably 0.01-0.1g based on 100g composition and the content of the hyaluronic acid or salt thereof is 0.001-1g, preferably 0.005-0.5g, more preferably 0.01-0.1g based on 100g composition.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to a pharmaceutical composition for home administration comprising superoxide dismutase and hyaluronic acid or a pharmaceutically acceptable salt thereof.

[Prior Art] Animals that live on land live by taking in oxygen from the air through breathing, but in humans, the radically active m elements generated from this oxygen attack cells and cause various disorders to the living body. For example, tissue disorder.

These include destruction of red blood cells, acceleration of libido peroxidation, promotion of platelet coagulation, and lymphocyte damage. Therefore, there are enzymes that convert this radical oxygen into 57) in the animal body, and superoxide dismutase (hereinafter referred to as SOD) is known as the most powerful enzyme among them.

Patent Application Publication No. Sho 62-501072 describes the use of this SOD to suppress chemical irritation of the skin, skin inflammation, or acne. however,
In the specification, chemical irritants such as lauryl sulfate 1-
The effects of lauric acid, cinnamaldehyde, benzoyl peroxide, sodium hydroxide, and eugenol on water, alcohol, and ether solutions have only been clarified; other than that, what effects do they have on skin inflammation and acne? is also not shown.

[Summary of the Invention] The present inventors have discovered the present invention as a result of studying pharmaceutical compositions for topical administration of SOD.

Thus, the present invention relates to a pharmaceutical composition for topical administration comprising SOD and hyaluronic acid or a pharmaceutically acceptable salt thereof.

The SOD used in the present invention may be human SOD or SOD obtained from animals such as cows, and these SODs can be obtained by conventionally used methods.

Furthermore, the hyaluronic acid used in the present invention may be obtained by biotechnology or obtained from animal bodies, for example, the hyaluronic acid. or ammonium salts. Japanese Unexamined Patent Publication No. 61-23
No. 6732 discloses a new topical medicament containing a pharmaceutically active substance and hyaluronic acid suitable for local administration. The pharmaceuticals disclosed in the specification are specifically ophthalmic pharmaceuticals, and there is no mention of other pharmaceuticals, and SOD is not listed as a pharmaceutically active substance.

The pharmaceutical composition of the present invention contains sOD and hyaluronic acid or a pharmaceutically acceptable salt thereof as active ingredients, and is prepared in a dosage form for home administration, such as an ointment, a gel, a lotion, a cream, a spray, a solution, an emulsion, etc. provided. The amount of SOD used is 0.001-1g per 100g of composition
Preferably 0.005 to 0.5g, more preferably 0.00g.
01-0.1g. Further, the content of hyaluronic acid or its pharmaceutically acceptable salt is 0 per 100 g of one composition.

001-1g, preferably 0.005-0.5g, more preferably 0.01-0.1g.

The composition of the present invention can be manufactured by mixing SOD and hyaluronic acid or a pharmaceutically acceptable salt thereof with a conventionally used base according to a conventional method for manufacturing compositions for topical administration. I can do it. Examples of additives that can be used are oily substances such as liquid paraffin, vaseline, silicone oils, aliphatic lower or higher alcohols, higher fatty acids.

Aliphatic esters, vegetable oils, castor oil, lanolin and its derivatives, squalane, squalene, etc.; emulsifiers/dispersants such as nonionic surfactants (polyhydric alcohol esters, polyoxyethylenes).

anionic compounds), gums, lecithin, etc.; wetting agents such as glycerin, ethanol, propatool.

sorbitol, amino acids, etc.; stabilizers such as antioxidants,
Preservatives, etc., and polyethylene glycol, polyethylene, repellent agents such as carboxymethyl cellulose, cellulose gel, polyvinyl alcohol, and the like. Taking the FLL aqueous ointment as an example, appropriate amounts of white petrolatum, stearyl alcohol, etc. are used as oil phase components, and appropriate amounts of propylene glycol, preservatives, water, etc. are used as water phase components. The composition of the present invention can be administered in an appropriate amount depending on the symptoms.
Apply to the affected area at least once a day.

The toxicity of the SOD used in the present invention is extremely low; for example, in acute, subacute, and chronic toxicity tests on mice, rats, guinea pigs, rabbits, dogs, cats, and monkeys, the toxicity of SOD was 4000 μ/k.
g (one time) and is safe in mice, rats, and monkeys.
It is safe to administer 1/kg for 30 days. Furthermore, it is safe to administer 12 μ/- to rats and monkeys for 12 months. On the other hand, the toxicity of hyaluronic acid is also extremely low; for example, the LDso (■/kg) of sodium hyaluronate is over 2400 (oral) and 4000 (subcutaneous) in mice, and over 800 (oral) and 4000 (subcutaneous) in rats. (subcutaneous), over 1000 (oral) in rabbits, 2000
That's all (subcutaneous).

The compositions of the present invention can be used to treat various skin diseases such as herpes simplex, bedsores, dry skin, melasma, freckles, and collagen diseases such as scleroderma, Behcet's disease, systemic lupus erythematosus, etc. Effective for skin diseases. In particular, it is a major feature of the present invention that it is effective when used to treat skin diseases caused by G therapy, for which there have been no effective measures in the past. “In the composition of the present invention, by adding hyaluronic acid to SOD, the resulting composition has moisturizing properties and smoothness compared to when using SOO alone, and also helps the SOD to penetrate into the skin. and can produce excellent results.

[Example] Next, an example of the present invention will be shown.

Example 1 +"'-"L
-1 ± 5 LSOD
0. 06 Sodium hyaluronate 0.05 Stearylyl alcohol 6 Isobrobyl myristate
2 Hexyldecanol 3 Liquid paraffin 10 White petrolatum
10J! Polyethylene tyrene-based non-ionic surfactant 6-polyvalent alcohol ester type non-ionic surfactant 3p-human U-methylbenzoic acid 3
0, IP-HydroO
Butyl benzoate 0.
1 Propylene glycol 12 Purified water was added to make 100 g. Using each of the above ingredients, a cream was produced according to a conventional method.

[Effects] The effects of the composition of the present invention obtained using the cream produced in Example 1 are shown.

(1) Sugi Q: 0 (29 years old, female) (herpes simplex) The cream of Example 1 was applied to the area where the blister formed on the left end of the lower lip had collapsed and had become film-like. The next day, the affected area dried up, and after one or two applications, the scab came off and the marks quickly disappeared.

Previously, if you contracted herpes simplex and used other drugs, it would take at least 7 to 10 days to fully recover.

(2) High oiAO (38 year old female) ('J Dermatitis) The cream of Example 1 was applied to treat skin hardening on the hands and face. From 3 to 4 days after application, one skin softening and one reduction in pigmentation were observed. Also.

Due to difficulty in opening the mouth due to skin hardening, the distance between the lips was 21, but within one week after application, the distance between the lips was 3.5 (!L) and the patient was able to eat.

(3) Tatsu Ohei (38 years old, male) (Birchiett's disease) The cream of Example 1 was applied to skin ulcers (3 locations) on the left shoulder joint and right lower leg. From the 5th day after application, the bottom of the ulcer began to swell significantly, and by the 100th day, a scab was attached to the surface of the affected area and it had healed.

(4) Hiro 0 Hiro 0 (31 years old, female) [stains, sparrow O
f (Freckles) The liver spots and freckles were severe, but when the cream of Example 1 was applied, they were significantly reduced in one week.

(5) Small 0, 0, 0 (67 m, male) (Decubitus rash) The cream of Example 1 was applied to paralysis of both lower limbs due to bone metastasis to the 12th vertebra due to prostate cancer, and cubitis in the sacral region. After application, the skin around the periphery of the pressure ulcer changed from dark brown to a normal color, and the expansion of the pressure ulcer area was prevented and reduced.

(6) Atsushi Nakao 0 (23 years old, female) (systemic lupus erythematosus) For several months of ribo-PG treatment for Chikuji's skin ulcer (left shoulder)
After E I therapy, the affected area was considerably reduced in size.

The ulcer base remained. When the cream of Example 1 was applied to this site once a day, the ulcer base rose from the 4th day and began to shrink rapidly, and turned into a pox scar from the 100th day.

(7) Kiri otaO (67 years old, female) (scleroderma) The cream of Example 1 was applied around one oral cavity because the facial skin had no hardening and trismus was also significant. The average distance between the upper and lower lips before application was 2.63, but after 10 days it was 3. l
Now that I'm al, it's easier to put my dentures in and take them out.

(8) Kameo Takao (60 years old, male) (scleroderma) The cream of Example 1 was applied to a site (5 x 3 cm) with significant skin hardening on the anterior chest. It became softer than other affected areas.

(9) Kazuo Yao (50 years old, male) (Inui-gai) I had severe dry skin, but when I applied the cream of Example 1, it improved after two weeks.

Claims (1)

[Claims] A pharmaceutical composition for topical administration comprising superoxide dismutase and hyaluronic acid or a pharmaceutically acceptable salt thereof.