JP2003119119A - Skin care preparation for anus - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a skin care preparation hardly providing frigid irritation in use and suitable for the therapy of hemorrhoid. SOLUTION: This skin care preparation for the hemorrhoid contains (1) a medicament and (2) >=70 wt.% glycerol. A local anesthetic, an antiphlogistine, a painkiller, a wound-healing agent, an antioxidant, a hemostatic or the like is preferably cited as the medicament. A nonaqueous gel preparation is preferably exemplified as a dosage form. A polyhydric alcohol such as 1,2-pentanediol and dipropylene glycol is prefarably included therein besides the glycerol. A carboxyvinyl polymer and/or a salt thereof, and a 10-30C alkyl ester of (meth) acrylic acid and/or a salt thereof are preferably exemplified as a gelatinizing agent. An organic amine is preferable as the alkali for the gelatinization.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a skin external preparation, and more particularly to a skin external preparation suitable for administration to the anus and its surroundings.

[0002]

2. Description of the Related Art External preparations for skin are often used for diseases on or near the skin because they have the advantage of being able to directly administer the drug to the affected area if the affected area is the skin or a portion very close to the skin. Typical dosage forms of such external skin preparations include lotions, creams, ointments, oil gel sticks, aqueous gels and the like. Among them, the aqueous gel contains no oily component other than the drug, and therefore has an advantage that clothes and the like are unlikely to be soiled with the oily component. In addition, the stickiness is the smallest in these preparations, and it can be said that it is a preferable dosage form as an external preparation for skin from the viewpoint of feeling of use. One of the major problems in such an aqueous gel preparation is a cold feeling during use. This is because the aqueous gel uses a large amount of an aqueous carrier having a good affinity with water and a relatively large specific heat. Therefore, in administration to a location where nerves are concentrated, such as the anus and its surroundings, this cold sensation often causes significant stimulation. Further, when the disease to be treated in the anus or its surroundings is hemorrhoidal, not only is the cold sensation painful and painful, but also the cooling during administration causes hemorrhoidal hemorrhage. It is said to have an unfavorable effect. For this reason, aqueous gel formulations have not been used much for the treatment of hemorrhoids.

On the other hand, no external preparation for skin characterized by containing 1) drug and 2) 70% by weight or more of glycerin has been known at all, and such external preparation for skin has a cold sensation upon administration. It has not been known at all that it is suitable for administration to the anus or its surroundings because it does not induce irritation or a factor that worsens the disease.

[0004]

The present invention has been made under such circumstances, and it is an object of the present invention to provide a skin external preparation suitable for treating hemorrhoids, which does not give a cold sensation during use. And

[0005]

In view of such a situation, the present inventors have made earnest research efforts to find a skin external preparation suitable for treating hemorrhoids, which does not give a cold sensation during use, The inventors have found that an external preparation for skin characterized by containing 1) a drug and 2) 70% by weight or more of glycerin has such properties, and completed the invention. That is, the present invention relates to the techniques described below. (1) An external preparation for skin, which comprises 1) a drug and 2) 70% by weight or more of glycerin. (2) The external preparation for skin according to (1), which is in the form of gel. (3) The external preparation for skin according to (1) or (2), which contains an organic amine salt of carboxyvinyl polymer. (4) The external preparation for skin according to (3), wherein the organic amine is triethanolamine. (5) It is characterized by containing substantially no water, (1)
(4) The external preparation for skin according to any one of (4). (6) The external preparation for skin according to any one of (1) to (5), which is applied to the anus and / or its periphery. Hereinafter, the present invention will be described in more detail.

[0006]

BEST MODE FOR CARRYING OUT THE INVENTION (1) Drug contained in the external preparation for skin of the present invention The external preparation for skin of the present invention comprises 1) a drug and 2) glycerin 70.
It is characterized by containing more than weight%. Here, as the drug that can be contained in the external preparation for skin of the present invention, any drug that is usually used for hemorrhoids can be used without particular limitation. For example, a local anesthetic, an antiphlogistic, and an analgesic. , Wound healing agents, antioxidants, hemostatics and the like can be preferably exemplified. Among them, the local anesthetics include aminobenzoic acid alkyl esters such as anestamine, tetracaine hydrochloride, aminobenzoic acid alkamine esters such as brocaine hydrochloride, dibucaines such as dibucaine hydrochloride, lidocaine, xylidines such as lidocaine hydrochloride. Preferable examples include oxybubrocaine hydrochloride, bupivacaine hydrochloride, mebipacaine hydrochloride, propitocaine hydrochloride, and oxysezaine. Of these, xylidines are preferable, and lidocaine and lidocaine hydrochloride are particularly preferable. Preferred examples of the anti-inflammatory agent include anti-inflammatory steroids such as cortisone, cortisone acetate, hydrocortisone, hydrocortisone acetate, and tetrahydrozoline hydrochloride, and nonsteroidal antihistamines. As the nonsteroidal antihistamine, diaminehydramine, ethanolamine antihistamines such as diphenhydramine hydrochloride, monoamine antihistamines such as chlorpheniramine maleate, phenothiazine antihistamines such as promethazine and mequitazine can be preferably exemplified, and among them, monoamine antihistamines are preferable. It can be illustrated, and chlorpheniramine maleate is particularly preferable. As analgesics, acetaminophenone, aniline analgesics such as phenacetin, anthranil analgesics such as mefenamic acid, diclofenac sodium, flufenamic acid, salicylate analgesics such as aspirin, choline salicylate, aminopyrine, antipyrine, sulpiline, etc. Pyrazolone analgesics, ibuprofen, naproxen, ketoprofen, fenbufen, and other phenylacetic acid analgesics can be preferably exemplified. As the antioxidant, tocopherol, tocopherol acetate, tocopherol nicotinate, ascorbic acid and the like can be preferably exemplified, and tocopherol is particularly preferable. Suitable examples of the wound healing agent include allantoin. Suitable examples of the disinfectant include chlorhexidine hydrochloride, chlorhexidine gluconate, and benzalkonium chloride. Among these disinfectants, chlorhexidine hydrochloride is particularly preferable. The preferred content of these agents in the external preparation for skin of the present invention is 0.01 to 10% by weight with respect to the total amount of the external preparation for skin for each agent,
More preferably, it is 0.05 to 5% by weight.

(2) Glycerin contained in the skin external preparation of the present invention The skin external preparation of the present invention comprises 1) a drug and 2) glycerin 70.
It is characterized by containing more than weight%. Here, the glycerin contained in the skin external preparation of the present invention, when the skin external preparation of the present invention is administered, solvates with water on the skin surface to generate heat of hydration, thereby imparting a warm feeling. Has the effect of In order to exert such effects, the amount of such glycerin is at least 70 relative to the total amount of the external preparation for skin.
A weight% is required, and a more preferable content is 75 weight% or more. Further, it is preferable that such glycerin is not hydrated. For this reason, it is preferable that the external preparation for skin of the present invention contains substantially no water. Here, "substantially free of water" means that water is not intentionally added, except for carry-over which the raw materials naturally contain.

(3) External preparation for skin of the present invention The external preparation for skin of the present invention comprises 1) a drug and 2) glycerin 70
It is characterized by containing more than weight%. The external preparation for skin of the present invention may contain, in addition to the above-mentioned essential components, the drug and glycerin, any component usually used in external preparations for skin. Such optional components include, for example, hydrocarbons such as squalane, liquid paraffin, and solid paraffin, silicones such as dimethicone and femethicone, esters such as jojoba oil and gay wax, and fatty acids such as stearic acid and oleic acid. , Higher alcohols such as behenyl alcohol, cetanol, oleyl alcohol, triglycerides such as beef tallow and olive oil, nonionic surfactants such as sorbitan sesquioleate, polyoxyethylene sorbitan monooleate, polyoxyethylene stearate, sodium lauryl stearate Anionic surfactants such as rate, cationic surfactants such as quaternary alkyl ammonium salts, polyhydric alcohols other than glycerin such as 1,3-butanediol, isoprene glycol and 1,2-pentanediol Kind,
Powders such as crystalline cellulose and cross-linked methyl polysiloxane, acrylic acid / alkyl methacrylate copolymer and / or its salt, carboxyvinyl polymer and / or its salt, thickeners such as xanthan gum and hydroxypropyl cellulose, vitamins and glycyrrhizin. Active ingredients such as and the like can be preferably exemplified. The external preparation for skin of the present invention is
As described above, since it is preferably an aqueous gelling agent, it is preferable to contain a gelling agent that forms such a gel. As such gelling agent, a carboxyvinyl polymer and / or a salt thereof can be particularly preferably exemplified. As the salt of the carboxyvinyl polymer, a salt soluble in glycerin as a base is preferable, and specifically, an organic amine such as triethanolamine can be preferably exemplified. The content of the carboxyvinyl polymer and the organic amine is preferably 0.05 to 5% by weight, more preferably 0.1 to 1% by weight, based on the total amount of the skin external preparation. It is also preferable that polyhydric alcohols other than glycerin such as 1,3-butanediol, isoprene glycol, and 1,2-pentanediol are contained, but polyethylene glycol is not contained in the polyhydric alcohols. preferable. Examples of preferable polyhydric alcohols other than glycerin include dipropylene glycol and 1,2-pentanediol. This is because heat generation due to hydration of glycerin is not impaired.
A preferable content of the polyhydric alcohol other than glycerin is 10 to 25% by weight in total. As a particularly preferred form, a form containing 10 to 20% by weight of dipropylene glycol and 3 to 8% by weight of 1,2-pentanediol can be preferably exemplified. This is because antisepticity can be obtained as a side effect in such a mixed form. The external preparation for skin of the present invention can be produced by treating these essential components and optional components according to a conventional method. Thus obtained external preparation for skin of the present invention is hydrated with water on the skin at the time of application and generates heat of hydration, so that there is no cooling sensation during application, and therefore diseases of the anus and its surroundings such as hemorrhoids. When applied to, it is possible to prevent cold sensation and retention of blood flow due to application cooling. Therefore, the external preparation for skin of the present invention is suitable for application to the anus or the surrounding area.

[0009]

EXAMPLES The present invention will be described in more detail below with reference to examples, but it goes without saying that the present invention is not limited to these examples.

<Example 1> The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention. Iglycerin 76.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0.1 parts by weight lidocaine hydrochloride 3 parts by weight carboxyvinyl polymer 0.4 parts by weight lotriethanolamine 0.3 parts by weight Department

Example 2 Anus of 10 ICR mice per group was fixed outside the body with an adhesive and sandpaper was rubbed against the anus to create a bleeding site. The specimen was applied to this bleeding site with a cotton swab, and the strength of the reaction was used to evaluate the strength of the stimulation of the bleeding site. The intensity of the reaction was measured by a video monitor as the amount of the animals that moved instantaneously at the time of application. As the samples, the skin external preparation of Example 1 and Comparative Example 1 in which 15% by weight of glycerin of the skin external preparation of Example 1 was replaced with polyethylene glycol 400 were used. The results are shown in Table 1. From this, it is clear that the external preparation for skin of the present invention causes less irritation to the bleeding part.

[0012]

[Table 1]

Example 3 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this was evaluated by the method of Example 2, the average movement distance was 3 ± 6 cm. From this, as a polyhydric alcohol other than glycerin, dipropylene glycol is 10 to 20% by weight, and 1,2-pentanediol is 3 to
It can be seen that the form containing 8% by weight is preferable. Iglycerin 76.2 parts by weight dipropylene glycol 5 parts by weight 1,2-pentanediol 15 parts by weight diisopropyl sebacate 0.1 parts by weight lidocaine hydrochloride 3 parts by weight carboxyvinyl polymer 0.4 parts by weight lotriethanolamine 0.3 parts by weight Department

Example 4 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the method of Example 2, the average migration distance was 6 ± 6 cm, which shows that it is preferable that the external preparation for skin of the present invention does not contain polyethylene glycol. Iglycerin 76.2 parts by weight dipropylene glycol 15 parts by weight polyethylene glycol 400 5 parts by weight diisopropyl sebacate 0.1 parts by weight lidocaine hydrochloride 3 parts by weight carboxyvinyl polymer 0.4 parts by weight lotriethanolamine 0.3 parts by weight

<Example 5> The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this is evaluated by the evaluation method of Example 2, the average migration distance is 3 ± 5 cm, and triethylamine can be used as the alkali for neutralizing the carboxyvinyl polymer. Therefore, the alkali is an organic amine. It turns out that it is preferable to use. Iglycerin 76.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0.1 parts by weight lidocaine hydrochloride 3 parts by weight carboxyvinyl polymer 0.4 parts by weight rotriethylamine 0.3 parts by weight

Example 6 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the evaluation method of Example 2, the average migration distance was 3 ± 6. As a gelling agent for the external preparation for skin of the present invention, an acrylic acid / methacrylic acid (C10-30) alkyl copolymer was also used. It turns out that it can be used. Iglycerin 76.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0.1 parts by weight lidocaine hydrochloride 3 parts by weight Pemulene TR-2 * 0.4 parts by weight lotriethanolamine 0. 3 parts by weight * Goodrich Co., acrylic acid / methacrylic acid (C10-30) alkyl copolymer

Example 7 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the evaluation method of Example 2, the average migration distance was 3 ± 4, and iglicerin 78.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0. 1 part by weight Hydrocortisone acetate 1 part by weight Carboxyvinyl polymer 0.4 part by weight Lotriethanolamine 0.3 part by weight

Example 8 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the evaluation method of Example 2, the average migration distance was 4 ± 5, and iglicerin 78.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0. 1 part by weight Chlorpheniramine maleate 1 part by weight Carboxyvinyl polymer 0.4 part by weight Lotriethanolamine 0.3 part by weight

Example 9 The external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the evaluation method of Example 2, the average migration distance was 4 ± 5, and iglicerin 78.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0. 1 part by weight Allantoin 1 part by weight Carboxyvinyl polymer 0.4 part by weight Lotriethanolamine 0.3 part by weight

<Example 8> An external preparation for skin of the present invention was prepared according to the following formulation. That is, each of the components a and b was heated to 80 ° C., the mixture b was added to a and gelled, and the mixture was stirred and cooled to obtain the aqueous gel external preparation for external use of the present invention.
When this product was evaluated by the evaluation method of Example 2, the average migration distance was 3 ± 5, and iglicerin 77.2 parts by weight dipropylene glycol 15 parts by weight 1,2-pentanediol 5 parts by weight diisopropyl sebacate 0. 1 part by weight Chlorpheniramine maleate 0.2 parts by weight Hydrocortisone acetate 0.5 parts by weight Tetrahydrozoline acetate 0.05 parts by weight Allantoin 1 part by weight Chlorhexidine hydrochloride 0.25 parts by weight Carboxyvinyl polymer 0.4 parts by weight Lotriethanolamine 0 .3 parts by weight

[0021]

According to the present invention, it is possible to provide a skin external preparation suitable for treating hemorrhoids that does not give a cold sensation during use.

   ─────────────────────────────────────────────────── ─── Continued front page    (72) Inventor Seiji Sugiyama             27-1 Takashimadai, Kanagawa-ku, Yokohama-shi, Kanagawa             Pola Kasei Co., Ltd. Yokohama Research Center F term (reference) 4C076 AA09 BB29 CC01 DD38W                       DD47 DD50Z EE09A EE23                       FF35 FF56 FF61

Claims (6)

[Claims] 1. An external preparation for skin, which comprises 1) a drug and 2) 70% by weight or more of glycerin. 2. The external preparation for skin according to claim 1, which is in the form of gel. 3. The external preparation for skin according to claim 1, which contains an organic amine salt of carboxyvinyl polymer. 4. The external preparation for skin according to claim 3, wherein the organic amine is triethanolamine. 5. The external preparation for skin according to any one of claims 1 to 4, which is substantially free of water. 6. The external preparation for skin according to any one of claims 1 to 5, which is applied to the anus and / or its periphery.