JPS60237018A - Composition having adhesivity to interior of oral cavity - Google Patents

Abstract

PURPOSE:The titled composition having more improved adhesivity, durability of adhesion state and sustained release properties than well-known pharmaceutical preparations, obtained by adding paste or a thickening agent and a drug to a well-known carboxyvinyl polymer as a base materialf for a dental analgesic. CONSTITUTION:A composition having adhesivity to the interior of oral cavity comprising >=20wt% based on total amount of the composition of carboxyvinyl polymer, 2-50wt% another paste or a thickening agent (e.g., CMC-Na, gum arabic, MC, etc.) and a proper amount of drug. All drugs applicable to the mucosa through the oral cavity may be used as the drug. For example, drugs for central nervous system, deodorants, remedy for stomatitis, etc. may be cited as the drug. This composition is formed into a shape such as a small-sized lamellar form, spherical form, etc. suitable for adhesion to the interior of the oral cavity. A carboxyvinyl polymer is used as a base material for having adhesivity to the interior of the oral cavity, and addition of the thickening agent or paste to it can regulate release and absorption rate of the drug.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to improvements in compositions that adhere to human oral mucosa and exhibit medicinal and other effects.

Attempts have been made for a long time to treat mucosal diseases such as stomatitis or to allow drugs to be absorbed into the body via the oral mucosa by attaching them to mucous membranes in the oral cavity. The principle of these drugs is sodium polyacrylate (Japanese Patent Laid-Open No. 51-38412), hydroxypropyl cellulose or polyethylene glycol (Japanese Patent Laid-open No. 4
9-133519) or polyacrylic acid or its t
l and hydroxypropylcellulose (JP-A-54-41
The main ingredient is a hydrophilic gel such as 320), which contains an appropriate drug.

However, when these inventions are actually tried again, none of them have the desired effect. For example, the latest and last invention has actually been implemented as an adhesive-type aphthous stomatitis treatment containing triamcimerone acetonide, but in addition to being difficult to adhere when actually applied to the oral mucosa.
It usually disappears within 2 hours, especially if you eat or drink after taking the medication. Therefore, sustained drug action, which is the main objective, cannot be expected very much.

In the first place, the purpose of this type of drug is to have the drug act for as long as possible through the oral mucosa, so a persistence of only about 2 hours is clearly insufficient for the purpose. The present invention uses hydrophilic polymeric materials that have not been previously utilized for oral adhesive compositions to provide novel oral adhesive compositions that have a much longer persistence than conventional oral adhesive compositions. The purpose is to

The inventors of the tree have been conducting systematic research on new formulations of R1 medicinal preparations, and as part of this research, they had previously made an invention in Japanese Patent Application Laid-Open No. 139415/1983, and discovered that carboxylic It has been discovered that a vinyl polymer (common name: carboxypolymethylene; trade name: CARBOPOL) is highly suitable as a gel dental analgesic base. This invention was subsequently commercialized as a dental analgesic under the trade name Konjisui Q.

However, as a result of subsequent research, the above carboxyvinyl polymer was not only excellent as a base material for dental analgesics, but also as a base material for oral preparations.
It has been found that by using this in combination with a thickening agent or a thickening agent, the release and absorption rate of the drug can be freely controlled.

According to the findings of the present inventor, it is difficult to mold carboxyvinyl polymer alone, but carboxymethylcellulose sodium, cellulose sodium glycolate, sodium alginate, gum arabic, gum tragacanth, guar gum, xanthan gum, tara gum, pullulan, etc. ,
Adding glue or thickeners for pharmaceutical preparations and food processing, such as methylcellulose, not only makes molding easier, but also increases the adhesion to the oral mucosa. By using commonly used excipients such as calcium carbonate and calcium silicate, the performance in combination with the main ingredient can be further improved.

Incidentally, in the composition of carboxyvinyl polymer and common excipients, due to the acidity of the carboxyvinyl polymer itself,
When the main ingredient is a basic substance such as an allocaloid, bioavailability is low, but it has been found that this drawback can also be improved by using a glue or thickener in combination. Table 1 below shows the results of experiments conducted by the inventor. Throughout each experiment, a dry tableting method was used to form the test preparations, and the tablets were compressed to a hardness of 20 on the Monsando hardness tester. The excipient used was approximately 0.
White sugar, excluding 3% calcium stearate (lubricant),
Lactose or glucose.

(The following is a blank space) In Table 1, sustainability in the experiment shown in Table 1 above was measured as follows.

The composition shown in the table above was prepared using a tablet making machine to a diameter of 9 mmφ and a thickness of 2 ml11. It was compressed into disc-shaped tablets with a hardness of 20 (Monsanto hardness scale) and a weight of about 150 mg. Separately, place a solution of 10 g of gelatin in 901 boiling water on a slide glass for 3 f.
A mucous membrane model was created by spreading and coagulating it to a fi-dimensional thickness.

Drop one drop of physiological saline on one side of the test tablet described above and press it onto the gelatin membrane described in Section 2.
The mixture was suspended in a beaker containing 0 ml of water and gently stirred from below using a magnetic stirrer. In this way,
The time taken for each test tablet to gradually soften and peel off from the slide glass was measured. Each experiment was repeated several times using the same tablet, and the average of the results was taken as the duration. The results are shown in Table 2 below.

Table 2 The results in Table 2 will naturally vary if the formulation or shape of the tablet changes, and the adhesion and swelling state will change, but it is easy to see that it is extremely long-lasting. In fact, when the test tablets were applied to the oral mucosa, adhesion lasting up to 8 hours or more was obtained. From this result as well, it is estimated that the composition of the present invention has excellent performance as an oral adhesive composition.

Next, in order to confirm the sustained release effect, which is another objective of the composition of the present invention, and in particular to confirm that the drug content is released at the same rate, the inventor conducted the following model experiment. That is, one test tablet was attached to each slide glass with a gelatin gel film used in the adhesion durability test, and then immersed in a beaker containing 100 ml of physiological saline at 37°C, and placed in a magnetic stirrer. While stirring, replace the physiological saline solution for the first 30 minutes, the following hour, and every hour thereafter, and remove any acidic dyes (such as food coloring red No. 3) and bases that have eluted into each physiological saline solution. The amounts of sex pigments (eg, tsuksin, methylene blue, etc.), vegetable pigments (carotene, sodium copper chlorophyllin, etc.), and other drugs were measured. The results for the test tablets AT, AY, and DT are shown in Figures 1 to 3. As is clear from the figure, the elution rate in each case reaches its maximum relatively quickly at first, then after a long maximum period, there is a tendency to gradually decrease, but in any case, the efficacy remains for a long time. It can be seen that.

Combining the results of the two experiments below, it can be concluded that the oral adhesive composition according to the present invention is one of the well-known formulations for intraoral administration in terms of adhesiveness, persistence of adhesive state, and sustained release properties. It is concluded that this product has superior performance to other formulations, and can be applied to various purposes in which sustained release through intraoral adhesion administration is expected.

The oral adhesive composition according to the present invention has good adhesion to the oral mucosa, and when a molded product of the composition is pressed against the inner surface of the cheek or lip area, it immediately adheres and remains in the area for a long time. It adheres to the inside and gradually releases the active ingredients such as medicines inside, and there is no risk of it disintegrating or peeling off even if you eat or drink it during the process. This point is extremely superior to conventional drugs of the same type.

The composition of the present invention may be shaped into a hemisphere, semi-ellipsoid, flat disc, flat ellipsoid, or other shape suitable for oral administration depending on the purpose. For molding, both dry methods (direct tableting method or indirect tableting method - e.g. slug method, rolling method, etc.) and wet methods can be used, but dry methods are used as much as possible, especially direct tabletting methods. It is better to use The size of the preparation may be small, with a diameter of ICl1 or less, so as not to give a foreign body sensation to the patient.

The drugs to be added to the composition of the present invention include all drugs that can be applied orally or vaginally, regardless of whether they are systemic or local. For example, drugs for the central nervous system such as antipyretic analgesics, drugs for peripheral nerves such as autonomic nerve agents, drugs for allergies such as antihistamines, drugs for the circulatory system such as antihypertensive agents, drugs for the respiratory system such as antitussives, drugs for treating stomatitis, Major examples include gastrointestinal drugs such as mouth fresheners or breath odor removers, metabolic drugs such as hormones, vitamins, antismoke agents or enzyme preparations, tumor treatment drugs, antibiotic preparations, and chemotherapy drugs. However, it is of course not limited to these.

As the excipient, conventional excipients such as white sugar, lactose, starch, dextrin, cyclodextrin, microcrystalline cellulose, etc. can be used; When incorporating an oily component such as dextrin or cyclodextrin, an inclusive excipient such as dextrin or cyclodextrin is preferable.

As the glue or thickener (adhesive component), as mentioned above, I. Lakanto gum, Colocin I. gum, Arahia gum,
Various natural gums such as guar gum, queen slant gum, taracum, xanthan gum, CMC sodium or cellulose derivatives such as methyl cellulose or cellulose sodium glycolate, sodium alginate, pullulan, etc. are used. The content of these ingredients in the composition is 2
~50% range.

As a lubricant, around 0.3% of calcium stearate or magnesium stearate, polyethylene glycol or talc is usually added. The use of appropriate amounts of lubricants often allows direct compression and improves productivity.

Carboxyvinyl polymer is usually added in a range of 25 to 40%. If the amount of this component is less than 20%, the desired sustainability will not be achieved sufficiently. Hereinafter, the mode of carrying out the invention will be described by way of examples, but the examples are of course for illustrative purposes only and do not mean a limitation on the spirit of the invention, and include a wide range of modifications depending on the purpose. One thing is obvious.

Example Carpoxyvinyl polymer (Carpopol 940) 4
After thoroughly mixing 0 g, CMC sodium 40 g, copper chlorophyllin sodium 2 g, menthol inclusion 17 g and calcium stearate 1 g, a total of 8 ffllllφ, thickness 0.8 mm, weight 180 mg, using a direct compression tablet making machine, Flat tablets with a hardness of 22 were manufactured.

The tablets listed below adhere well to the mucous membranes in the oral cavity, but because they are small, they hardly give the user the sensation of a foreign body. And not only can it eliminate 11 odors for a long time of 5 to 7 hours, but it also provides a pleasant refreshing feeling to the person who uses it! It is an ideal mouth freshener.

[Brief explanation of drawings]

Figures 1 to 3 show "1" produced using the composition of the present invention.
It is a graph showing the elution of different drugs from the intracavitary injection 1j-river preparation. Horn g/% 0 12349 56 Time sword 2 Zudo g/% 0 1 2 8 4, 5 6 11, City 11

Claims (1)

[Scope of Claims] 1] Oral adhesive, characterized by containing 20% or more of a carboxyvinyl polymer, 2 to 50% of other glue or thickener, and an appropriate amount of a drug in the entire composition. Composition. [2] The composition according to claim 1, wherein the drug acts mucosally or transmucosally to remove or mask dirt or oral odor. (3) The whole is small plate-like, spherical, conical, ellipsoidal,
3. The composition according to claim 1 or 2, which has a toroidal shape or other shape suitable for adhering to the inside of the mouth. 14 [The composition according to any one of claims 1 to 3, wherein the drug is gradually released from the composition.