JPS6043328B2 - ointment base - Google Patents

Description

[Detailed description of the invention] The present invention adheres to moist mucosal or dermal surfaces.

ointment base. Powder, liquid, or ointment forms have traditionally been used as therapeutic agents for human skin, but they have special compositions for moist surfaces or moist mucous membrane surfaces (for example, oral mucosal surfaces, etc.). Ointment is used.

Ointment (medicinal) products applied to such wet surfaces generally contain sodium carboxymethyl cellulose (hereinafter abbreviated as CMC) in an oily base (main ingredient) such as petrolatum.
The base material is a mixture of thickeners with adhesive or viscous properties, such as, and a pharmaceutical ingredient [a preferred example is dexamethasone (0.1%), a synthetic adrenocortical hormone]. It is something that can be done. In addition to petrolatum, liquid paraffin or a mixture of these is used as an oily base (main ingredient).
Paraffinic hydrocarbons such as Plasty Base (trade name) (Showa Yakuhin KK Sales 1), which is made by adding liquid paraffin with polyethylene, are mainly used, and CM is used as a thickener.
In addition to C, dextrin, gum arabic, sodium alginate, sodium polyacrylate (hereinafter abbreviated as PAN), pectin, gelatin, methyl cellulose (hereinafter abbreviated as MC), hydroxypropylcellulose (hereinafter abbreviated as ■℃) , polyvinyl alcohol, etc. are used. Existing technology is JP-A-51-
There is an invention in Publication No. 384, and the main part of the invention described in the claims uses an oily compound such as vaseline and PAN as a thickener, and if necessary, a binder and a coloring agent. , is described as an ointment base mixed with a lubricant, flavoring agent, or flavoring agent, and an example of an ointment base mixed with 60 g of vaseline and 30 fl of PAN is described in Examples. The existing technology is characterized by PAN's excellent dispersion, adhesiveness, and thickening properties, which allow it to adhere strongly to localized areas, and after swelling, the formulation gradually dissolves, and the drug contained therein is eluted almost uniformly. It is stated that. What must be considered in this example of existing technology is the amount of PAN mixed in the ointment base, and the amount of sodium ions in PAN is quite large, so the drugs that can be blended are restricted and are therefore contraindicated. Anticipated drugs include tetracyclines, which tend to have negative effects on drugs that form salts with acids. Furthermore, since PAN gives a unique strong slimy feeling when used in the oral cavity, improvements in the tactile aspect have been desired. The present inventors have conducted various studies on the above points, and found that it contains inorganic ions, has good miscibility with oily bases (base ingredients), adhesives, and pharmaceutical ingredients blended with these, and has excellent dispersibility. To create a white, translucent ointment base that has strong adhesion when applied to a wet surface, has an excellent application feeling, does not feel slimy in the oral cavity, is tasteless, non-irritating, and is ointment base. Successful.

It is therefore an object of the present invention to provide such an ointment base. Another advantage of the present invention is that the ointment base achieves the above-mentioned excellent properties. Specifically, the ointment base of the present invention uses an oily base such as petrolatum, plasty base, or liquid paraffin as a paraffinic hydrocarbon compound as a main ingredient (first component), and as an auxiliary agent (second ingredient). It is produced by using carboxyvinyl polymer (hereinafter abbreviated as CVP) and further mixing and kneading a thickener as a third component. Next, details of the configuration of the present invention will be explained.

As for the oil base, known oil bases may be used alone or in combination as described above. In the ointment base of the present invention, the content of the main oil base in the total base is practically 60 to 8.
Saliva volume%.

CVP, which is an auxiliary agent, is a copolymer of acrylic acid and allylated polyhydric alcohol, and the addition of this CVP is a feature of the present invention.

CVP is a white powder that swells immediately upon contact with water and gradually dissolves. According to the Ministry of Health and Welfare's "Standards for Cosmetic Raw Materials," the detailed chemical structure of CVP has not been clarified;
No. 41 and U.S. Pat. No. 2,798,053 (1957
) Based on the specification, it is thought to be mainly a copolymer of acrylic acid and a small amount of allyl sucrose, and the molecular weight is 10 to 30.
It is a defense. In the Merc Index (W edition), it is described as carboxypolymethylene, commonly known as Carbobol (accurately speaking, it is the trade name of a product made by Gudryutsch). The CVP commercially available product suitably used in the present invention is manufactured by Wako Pure Chemical KK...
■ISWAKO8. In the prior art, CVP has been used as a unique thickening substance by making a salt with a basic substance exclusively in an aqueous system or aqueous phase, but in the present invention, the bulk powder can be used for flavor processing. No direct suspension in an oily base was performed. That is, according to the inventors, C
VP has excellent dispersibility, that is, it increases the miscibility of oily bases (base ingredients) such as vaseline with thickeners and pharmaceutical ingredients, improves the mutual dispersibility of these tissues, and at the same time makes it easier to apply to wet areas. The medicinal component is uniformly dispersed and retained so that spontaneous release of the medicinal component occurs gradually when the drug is released.
This increases the medicinal effect. These characteristics are CVP
It is thought that this is because a polar group such as -COOH or -0H that contributes to adhesion and dispersibility is present in the molecule of the adhesive, suppressing the hydrophilicity of the one-sided adhesive. Furthermore, since CVP is not bound to inorganic metal salts, there is little risk of causing any inconvenience in interaction with prescribed pharmaceutical ingredients. This is also one of the major features of the present invention. The amount of CVP added is at least 2% by weight, preferably 5% by weight in the ointment base.
It is desirable that the amount is around 2% by weight or less, and no improvement in tackiness is observed even if it is used at 1% by weight or more, so it is considered undesirable in terms of cost. It's the economy. As the thickening agent compounded as the third essential component in the ointment base of the present invention, the conventional thickener is
Although almost all known thickeners can be used, research by the present inventors has shown that cellulose derivatives such as CMClMClHPC are suitable, with MC being particularly suitable.

It is desirable that the amount added be at least 1% by volume or more, preferably around 2% by volume, in the ointment base, and the above C.
It has the function of adjusting the consistency of the ointment base by blending with the VP and the oily base, and can be in an amount of approximately 15-3% by weight. The thus obtained oily base + CV
The ointment base of the present invention, which consists of three essential components of P+ Cellulonos derivatives (however, the total of the three does not exceed 10% by volume), is white, translucent, tasteless, odorless, and nonirritating, and is formulated to be Not only does it have fewer inconveniences with other drugs, but it also has excellent adhesion to moist affected areas and retention at the adhering site, and does not cause an unpleasant slimy feeling when applied to the oral cavity.

In this way, the medicinal component is reliably and gradually released in the affected area, and the medicinal effect lasts for a long time.

The drugs used as pharmaceutical ingredients include hormones such as insulin and steroid hormones, antibiotics such as tetracycline, oxytetracycline, and aminobenzylpenicillin, and disinfectants such as chlorhexidine, iodine pyrrolidone, azulene, and copper sodium chlorophyll. Example 1 Plastybase-50W (trade name) 60.9y1 carboxyvinyl polymer 3f and methylcellulose 27y
The ointment base of the present invention was prepared by thoroughly mixing the ingredients in a kneader.

Separately, prednisolone 0.1V and Plastybase-50W99 are sufficiently kneaded together as a medicinal ingredient, and this is added to the above ointment base, mixed by vacuum stirring, and filled into a tube to form a medicinal product. An ointment product is obtained.
Example 2 An ointment base of the present invention was prepared by thoroughly mixing 60.9 g of Plastybase-50W, 6 y of carboxyvinyl polymer, and 20 y of hydroxypropyl methyl cellulose using a crusher.

Add to this 0.1 triamcinolone acetonide (pharmaceutical ingredient)
A medicinal ointment product can be obtained by mixing y evenly throughout and dispensing it into tubes each weighing 5 g. Example 3 Pharmacopoeia Vaseline 99, Microcristan Wax 25y
1. Liquid paraffin 60y and dextrin fatty acid ester 6y are heated in an oil bath to 120°C, dissolved and mixed well, and cooled to about 30'C to form an oily base.

This oil base 76.9y1 carboxyvinyl polymer 3
By mixing V and pharmacopoeial carboxymethyl cellulose Na2Oy to make the entire quality uniform, this. An inventive ointment base was prepared. At this time, a pharmaceutical ointment product can be obtained by simultaneously mixing 0.1 y of pharmacopoeial dexamethasone (a pharmaceutical ingredient) and filling the mixture into a tube. The ointment base of the present invention produced according to the above examples provides an ointment (medicinal) product in which the oily base, adhesive, and pharmaceutical ingredients contained therein have good mutual miscibility and excellent dispersibility. When applied to wet surfaces, it has a strong adhesive force, provides an excellent application feeling, and does not have a slimy feeling in the oral cavity, and is tasteless and non-irritating.

Test Examples The ointment product obtained in Example 3 contains 99.9f of ointment base and 0.1y of dexamethasone (a). 1% by weight
).

The main drug (dexamethasone) content of this product is as dilute as 0.1%, so it is difficult to apply it to living organisms (experimental animals) and measure the concentration of the main drug in the blood of that individual. Experiments can be conducted using pharmacological effects (granuloma formation suppressive effect or capillary permeability suppressive effect) as indicators, and the absorption status of the main drug can be indirectly shown. A group of eight male hamsters were given sterile cotton balls (15±1 Tf) in their cheek pouches.
Lg) is inserted to cause inflammation, the cotton ball and the granulation tissue surrounding it are removed, and the granuloma (Lg) is calculated by subtracting the weight of the cotton ball from the dry weight.
The dry weight was measured for the left cheek pouch (control) and the right cheek pouch (the product was applied to the mucous membrane) 6 days after the start of the test [cotton pellet method (Reference: Tamura, Fujii: Pharmacology and Treatment Vol.
．． lO, NO. l2, 6693-6697, 1982)
].

Claims (1)

[Claims] 1. Paraffinic hydrocarbon compound 60-8 as the main ingredient
0% by weight, 2~2% of carboxyvinyl polymer as auxiliary agent
10% by weight of a thickener and 10-30% by weight of a thickener, provided that the total of the three does not exceed 100% by weight. 2 The paraffinic hydrocarbon compound as the main ingredient is vaseline, microcrystalline wax, solid paraffin,
2. The ointment base according to claim 1, wherein the ointment base is a liquid paraffin or a mixture thereof. 3. The ointment base according to claim 1, wherein the carboxyvinyl polymer as an auxiliary agent is a copolymer of acrylic acid and allylated polyhydric alcohol. 4. The ointment base according to claim 1, wherein the thickener is a cellulose derivative.