JP2016138066A - Dental caries remover - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a dental caries remover which can be used safely without causing damage or irritation to an oral tissue such as a periodontal soft tissue or a tooth tissue, the dental caries remover having excellent preservation stability and a good feeling in use.SOLUTION: A dental caries remover comprises bromelain and limonene, the dental caries remover comprising macrogol or gelated hydrocarbons as a base.SELECTED DRAWING: None

Description

  The present invention relates to a caries portion remover.

  When a tooth is carious, it is a common treatment method to scrape it off using a rotary cutting tool. However, there is a problem that the patient feels a fear because vibration and sound of the instrument are generated during the treatment, and pain is induced by heat generated by applying pressure to the tooth surface during the work. Also, there is a possibility that even healthy dentin that does not need to be cut may be removed, or in the case of deep caries, pulpitis may be induced by excessive tooth removal operation. Has been. If the caries site is soft, it can be removed with a dental instrument called an excavator, but it is difficult to remove completely.

  In this way, instead of the conventional method of removing caries, a method for selectively removing carious dentin with a tool after softening the soft dentin with a chemical agent to facilitate removal is proposed. This method is called a chemical-mechanical caries removal method.

  For example, a method of removing carious dentin that has been dissolved using a caries remover developed in Sweden and softened with a dedicated device is used (trade name “Carisolv®” (Carisolv), Medi Team) No. 2,728,306, Non-Patent Documents 1 to 5). However, carisolve has a problem that the caries dentin has a weak softening ability and takes a long time for treatment, and it requires a mixing step before use, is complicated in operation, and has disadvantages such as poor storage stability. is there. Furthermore, even though it contains a small amount of sodium hypochlorite (0.5%), there are concerns about safety to the living body such as gingival damage, the risk of inhibiting the polymerization of the composite resin, and the drug itself is expensive. It is not widely used clinically.

  As a dental caries remover that does not contain sodium hypochlorite, the caries remover disclosed in Patent Documents 2 and 3 is known, and further, it is a preparation using papain, a constituent enzyme of papaya. Papacarie is sold in Brazil and is applied clinically mainly in South America. However, most reports indicate that papacarier has only the same caries removal effect as carisolve.

  Recently, Yamada et al. Used caramel removal using orange oil (main component: limonene) to efficiently remove softened organic matter using bromelain, a cysteine protease contained in pineapple, instead of papaya. Agents have been proposed (Non-Patent Documents 6 and 7). This caries remover does not contain sodium hypochlorite and is safe because it uses plant-derived ingredients that are safe for the body. There is no need to avoid. In addition, when carisolve is used, the removal of carious dentin, which takes an average of 8 to 10 minutes, can be completed within an average of 6 to 7 minutes, so the time required for caries removal can be shortened. There is. It also has an excellent feature that dentine does not break or crack on the cavity surface after removal of caries.

  However, the above caries remover using bromelain (BO reagent disclosed in Non-Patent Document 6: bromelain 10%, orange oil 10% or 20%, xanthan gum, polyoxyethylene hydrogenated castor oil, edible red, ethyl (Including parabens) has problems with stability, and since it has a unique taste and smell when mixed with orange oil, further improvements are required.

Patent 2,728,306 JP 2005-289924 International Publication WO 2004/45594

J. Clin. Pediatr. Dent., 37, pp.183-187, 2012 J. Clin. Pediatr. Dent., 35, pp.75-79, 2010 J. Clin. Pediatr. Dent., 31, pp.199-201, 2007 J. Dent., 36, pp.130-137, 2008 J. Clin. Pediatr. Dent., 30, pp.121-126, 2005 Japanese Dental Preservation Journal, 54, pp.142-152, 2011 Journal of Laser Dentistry, 22, pp.85-92, 2011

  An object of the present invention is to provide a caries removing agent that can soften and remove carious portions in a short time. Another object of the present invention is a caries remover that can be used safely without causing irritation or injury to oral tissues such as periodontal soft tissues or dental tissues, and has excellent storage stability and usability. It is to provide a pesticide remover.

  As a result of earnest research to solve the problems of the BO formulation disclosed in Non-Patent Documents 6 and 7, the present inventors used limonene instead of orange oil, and changed to xanthan gum as a base. It has been found that by using macrogol or gelled hydrocarbon, a caries remover excellent in storage stability and feeling of use can be provided without impairing the property of softening the carious portion in a short time. The present invention has been completed based on the above findings.

  That is, the present invention provides a caries remover containing bromelain and limonene, and a caries remover containing macrogol or gelled hydrocarbon as a base.

  According to a preferred embodiment of the present invention, there is provided the above caries remover that does not contain orange oil; the above caries remover that does not contain water; and the above caries remover that does not contain xanthan gum.

  According to a further preferred embodiment of the present invention, there is provided a caries remover comprising bromelain and limonene, comprising the macrogol as a base and further comprising polyoxyethylene hydrogenated castor oil (60). Provided.

  According to still another preferred embodiment of the present invention, a caries remover comprising bromelain and limonene, comprising the gelled hydrocarbon as a base and further comprising a sucrose fatty acid ester; and A caries remover comprising bromelain and limonene, comprising the gelled hydrocarbon as a base, and further comprising the sucrose fatty acid ester and hydroxypropylmethylcellulose; and the polyoxyethylene hydrogenated castor oil None of the above caries removers are provided.

  From another aspect, according to the present invention, there is provided a method for dissolving a carious part, comprising the step of bringing a composition containing bromelain, limonene and a macrogol or gelled hydrocarbon as a base into contact with the carious part. Is provided. From yet another aspect, the present invention also provides the use of bromelain, limonene, and macrogol or gelled hydrocarbons as a base for the manufacture of caries removers.

  Since the caries remover of the present invention softens the dentin of the caries part in a short time and can easily remove the caries part with a commonly used instrument, it is compared with the conventional caries remover. The time required for the removal operation of the eroded portion can be shortened. In addition, since the caries remover of the present invention does not contain sodium hypochlorite, it can be used safely without causing irritation or injury to oral tissues or tooth tissues such as periodontal soft tissues, Since it contains limonene instead of orange oil, it also has an excellent usability. Furthermore, the caries remover of the present invention is excellent in storage stability, and has a feature that it is difficult to cause a decrease in efficacy due to decomposition, particularly in storage at a distribution stage, dental clinic or hospital.

  The caries remover of the present invention contains bromelain and limonene, and is characterized by containing macrogol or gelled hydrocarbon as a base.

  Bromelain is a cysteine protease contained in pineapple (Ananas comosus), and a commercial product extracted from pineapple stems can be easily obtained. In general, the isoelectric point is pH 9.55, showing activity at pH 3 to 10, and optimal activity at pH 5 to 8. However, bromelain that can be used for the caries remover of the present invention is the above-mentioned specific one. It is not limited to bromelain.

  As limonene (1-methyl-4- (1-methylethenyl) cyclohexene), any of d-form, l-form, and racemic form may be used, but d-limonene can be preferably used. Although d-limonene is contained in a large amount in orange oil, when orange oil is used instead of limonene, there is a problem that the taste and smell deteriorate. Therefore, it is preferable to use purified limonene in the caries remover of the present invention.

  The caries remover of the present invention contains macrogol or gelled hydrocarbon as a base. The caries remover containing macrogol is provided as a creamy water-soluble composition, and the caries remover containing gelled hydrocarbons is provided as an ointment-like oily composition. Therefore, the caries remover of the present invention is provided as a water-soluble composition or oil-based composition so as to contain either macrogol or gelled hydrocarbons depending on the purpose of use or use site. However, in some cases, the macrogol and the gelled hydrocarbon can be mixed and used as necessary.

  As macrogol (polyethylene glycol), Macrogol 400, Macrogol 1500, Macrogol 4000, Macrogol 8000, etc., generally listed in the Japanese Pharmacopoeia, are used alone or as a mixture of two or more. can do. When the caries remover of the present invention is prepared as an oily composition, it is preferable to use a mixture of Macrogol 400 and Macrogol 4000. The ratio between the macro goal 400 and the macro goal 4000 is not particularly limited. For example, the macro goal 400 and the macro goal 4000 can be used so that the weight ratio thereof is about 1: 1 to 3: 1.

  The gelled hydrocarbon is obtained by gelling liquid paraffin with 5 to 10% amount of polyethylene. Generally, a gelled hydrocarbon listed in the standard for pharmaceutical additives can be used.

  The proportion of bromelain, limonene, macrogol as a base or gelled hydrocarbon in the caries remover of the present invention can be appropriately selected according to the purpose of use and the site of use. Bromelain is 5 to 15% by weight, preferably 10% by weight, limonene is 10 to 30% by weight, preferably 15 to 25% by weight, and particularly preferably 20% by weight. 50 to 80% by weight, preferably 60 to 70% by weight, or gelled hydrocarbon to be 30 to 70% by weight, preferably 40 to 50% by weight Can do.

  In the caries remover of the present invention, if necessary, polyoxyethylene hydrogenated castor oil or polysorbate as a solubilizer, sucrose fatty acid ester, glyceryl stearate, sorbitan monooleate, polyethylene glycol stearate as a release agent For example, hydroxypropyl methylcellulose can be added as a thickener. Polyoxyethylene hydrogenated castor oil is preferably added when the caries remover of the present invention is prepared as an aqueous composition. For example, polyoxyethylene hydrogenated castor oil (60) is added to the total weight of the composition. It can be added at a ratio of about 3 to 10% by weight, preferably about 5% by weight. The release agent and thickener are preferably added when the caries remover of the present invention is prepared as an oily composition. For example, sucrose fatty acid ester is 5 to 20% by weight, preferably about 5 to 15% by weight with respect to the total weight of the composition, and hydroxypropylmethylcellulose is 5 to 30% by weight with respect to the total weight of the composition, preferably It can mix | blend in the ratio of about 10 to 20 weight%.

  The caries remover of the present invention can be prepared without using water by kneading the above components by an appropriate method, but a small amount of an organic solvent may be added if necessary. Examples of the organic solvent include ethanol, glycerin, ethylene glycol, and the like. If necessary, the caries remover of the present invention includes coloring agents such as food red and red perilla polyphenol, preservatives such as ethyl paraben, chelating agents such as disodium edetate, inorganic metal salts such as sodium chloride, phosphorus One or more organic acids such as acids and tartaric acid, bacteriolytic enzymes such as egg white lysozyme and pectinase, surfactants such as cetrimide, pH regulators, buffers and osmotic pressure regulators can be blended. The caries remover of the present invention can also be prepared as a semi-solid having gel properties and thixotropic properties by adding an appropriate formulation additive such as a gelling agent as necessary.

  The usage mode of the caries remover of the present invention is not particularly limited. For example, a technique such as applying a small amount of caries remover to a flat head filling machine or an excavator and applying it to the caries portion can be adopted. However, this technique is not particularly limited. After application, a part or the whole of the caries portion dissolves within a few minutes, and can be completely removed using a normal instrument such as an excavator.

  An example of a caries removal procedure using the caries remover of the present invention is specifically shown in Example 6 of the example, but the procedure shown in Example 6 is an example and is used by the practitioner or used It goes without saying that appropriate alterations and modifications can be made according to the instruments and devices. Generally, caries remover is applied to the carious tooth surface, and after 30 seconds of application, caries dentin can be removed with a dental instrument such as an excavator or a low-speed round bar. It is possible to remove carious dentin as a lump. If necessary, the caries remover may be applied again to completely remove caries. If caries are present at the enamel margin, it is desirable to remove them with a low speed round bar prior to treatment with the caries remover. In general, the determination of caries removal can be completed by confirming a state in which no staining is observed in the cavity after caries removal using a caries detection liquid.

  As used herein, “dissolution of caries” or its synonym includes not only the phenomenon of caries being dissolved macroscopically, but also the phenomenon of caries being softened by micro dissolution of caries. Must be interpreted in the broadest sense, and should not be limited in any way. For example, it is included in the concept of caries dissolution to suppress caries formation by dissolving and removing caries at the initial stage of formation. Moreover, since the caries removing agent of the present invention has the effect of promoting the removal of gingival marginal calculus, it can be used in the same manner when removing calculus for the prevention of caries. This aspect is also included in the usage aspect of the caries remover of the present invention. Furthermore, the caries remover of the present invention can be used for humans or non-human mammals.

EXAMPLES Hereinafter, although an Example demonstrates this invention further more concretely, the scope of the present invention is not limited to the following Example.
Example 1: BO prescription (comparative example)
Bromelain (10.0 g) was added to purified water (58.4 g), and the mixture was stirred well with a vortex mixer. After adding orange oil (23.6 g) and stirring, polyoxyethylene hydrogenated castor oil (10) (5.0 g) was added and further stirred. Next, ethyl paraben (2.0 g) was added and stirred, and then xanthan gum (1.0 g) was added and stirred until uniform and stored in a glass container.

Example 2: Formula 1 with a water-soluble base (invention)
Macrogol 400 (39.0 g) and polyoxyethylene hydrogenated castor oil (60) (5.0 g) were added to Macrogol 4000 (26.0 g) heated to 65 ° C., and kneaded for 1 hour with a crusher. The mixture was allowed to cool to room temperature, bromelain (10.0 g) was added, and kneaded for 5 minutes. Next, limonene (20.0 g) was added and kneaded for 5 minutes, and further kneaded for 1 hour and stored in a glass container.

Example 3: Formula 2 with an oily base (invention)
Sucrose fatty acid ester (10.0 g) was added to gelled hydrocarbon (46.0 g) and kneaded for 2 minutes, and then hydroxypropylmethylcellulose (hypromellose, 14.0 g) was added and kneaded for 3 minutes. Bromelain (10.0 g) was added and kneaded for 3 minutes. Subsequently, limonene (20.0 g) was added and kneaded for 3 minutes, and then kneaded for another 10 minutes and stored in a glass container.

Example 4: Stability test The caries remover prepared in Examples 1 to 3 was stored at 15 ° C and 30 ° C (75% RH) and evaluated for color and odor at the start of storage, after 2 weeks, and after 4 weeks. did. Table 1 shows the storage results at 15 ° C., and Table 2 shows the storage results at 30 ° C. (75% RH).

  The BO formulation had a pale yellow color due to the influence of yellow orange oil, with a very light brown bromelain color. On the other hand, in Formula 1 and Formula 2, since limonene was transparent, the color of bromelain itself was very light brown. Although there were differences in color due to differences in ingredients at the start, all formulations showed a uniform color. After 2 weeks of storage at 15 ° C., the BO formulation showed a yellow layer (oil layer) separation on the top, whereas Formulas 1 and 2 did not show such separation. When stored at 30 ° C-75% RH for 2 weeks, the BO formulation showed significant separation of the oil and water layers and insolubilization of bromelain and xanthan gum in the water layer. Moreover, while there was thickening at the start, it changed into a liquid without thickening because xanthan gum became insoluble. Four weeks later, bromelain and xanthan gum were further insolubilized. On the other hand, Formula 1 and Formula 2 maintained the same appearance as at the beginning both after 2 weeks and after 4 weeks.

Regarding odors, orange oil and limonene smelled strongly in both formulas at the start, but when stored at 15 ° C, the BO formula and formula 1 had a slight odor of orange oil and limonene over time. It became dull. In addition, under the storage conditions of 30 ° C-75% RH, the limonene odor only faded with the prescription 1, whereas with the BO prescription, the odor of orange oil almost disappeared over time, and the smell of bromelain was unpleasant. It changed to an odor mixed with odor. There was no change for Formula 2 under either storage condition.
From the above results, it is clear that Formula 1 and Formula 2 can store bromelain and limonene, which are active ingredients, more stably than the BO formulation.

Example 5: Sensory test The caries remover produced in Examples 1 to 3 was applied to the teeth of healthy individuals to evaluate taste and odor.
In terms of odor, the BO formulation did not completely mask the specific odor of the bromelain enzyme by orange oil, and changed to an unpleasant odor that differed from the orange odor over time after preparation. On the other hand, the specific odor of bromelain enzyme was masked in the formulations of Examples 2 and 3, and the orange odor was maintained especially in the formulation of Example 3.
As for taste, all the formulations had citrus bitterness and slight irritation, but they acted on the tooth surface during treatment and gargle after treatment, so the patient felt very little. In both prescriptions of Examples 2 and 3, the caries removal treatment time was shortened compared to the BO prescription. Since BO formulation is a low viscosity solution, it flows when applied to the cavity or carious tooth surface, and the operability is not good, but the formulations of Examples 2 and 3 are inserted because they are ointment or gel It is easy to apply and adheres to the tooth surface. The patient had a faint orange odor at the time of treatment.

Example 6: Caries removal
(a) How to apply caries remover Apply caries remover to carious cavity surface and start caries removal 30 seconds after application. Although the caries remover is applied to the carious dentin, there is no problem even if the carious remover is applied to the healthy dentin. Enamel ivory and axillary margins tend to leave behind carious dentin and should be applied carefully. Since enamel caries, which are mostly inorganic components, cannot generally be expected to have an effect, caries are removed using enamel caries using rotary cutting tools such as diamond points and round bars. Should.

(b) Removal of carious dentin Caries removal using a hand cutting instrument is basically performed under anesthesia. A caries remover is applied to the carious cavity surface, and after 30 seconds, caries dentin is removed using a hand cutting device such as an extractor, spoon extractor, and carisorb dedicated hand caries remover. If it is felt that the operation efficiency of caries removal has been lowered, the cavity surface can be washed with water, dried with air, and then the caries remover can be applied again to the cavity surface. The treatment may be continued by adding a caries remover without washing, but the action may be reduced if there is an old drug left, so wash and dry as much as possible before reapplying. Is desirable. After re-application, the caries removal may be resumed without waiting for 30 seconds. This operation is repeated several times until the carious dentin removal is completed.

  When using an electric engine and a rotary cutting tool together, apply a caries remover to the carious cavity surface and leave it for 30 seconds, then attach a round bar made of stainless steel or the like to the electric engine and place it in the cavity. Remove carious dentin. When removing caries, it is usually performed without anesthesia, but if pain occurs during the procedure, anesthesia may be performed. At first, it is performed without applying cold water or the like, but the carious dentin is removed as a large lump, so the soft dentin attached to the bar with gauze is removed at the key points. When using a rotary cutting tool, it should be used at medium and low speeds. Since the carious dentin softens and adheres to the round bar, the carious dentin softened with gauze or the like is frequently removed, and a new caries removing agent is added to the cavity. Prior addition of water is not necessary. Usually, the removal of carious dentin is completed by adding frequently about 2-3 times.

  When removing carious dentin using an Er: YAG laser, the carious dentin removal effect is improved by applying a carious tooth removal agent to the cavity surface in advance. Time can be shortened. Apply caries remover to the cavity surface and irradiate Er: YAG laser 30 seconds later. As the laser irradiation conditions, the conditions indicated for each laser can be selected. Caries are removed while lightly contacting the cavity surface under water injection with an irradiation power of around 80mJ.

  If the cavity surface is irradiated with a Nd: YAG laser or the like after applying the caries remover, the carious dentin removal effect may be improved. A caries remover is applied to the cavity surface, and after 30 seconds, a drop of black ink or the like is dropped on the cavity surface, and then the cavity surface is irradiated with an Nd: YAG laser at an output of 100 mJ and 20 PPS. Alternatively, black ink or the like may be mixed with the caries remover before applying the BO reagent to the cavity surface. At that time, the tip of the laser fiber is brought into contact with the cavity surface and irradiated for 5 seconds. Laser irradiation can be performed while air is being applied to the cavity surface in order to avoid a rise in the temperature of the cavity surface.

Claims (5)

A caries remover containing bromelain and limonene, which contains macrogol or gelled hydrocarbon as a base. The caries remover according to claim 1, which does not contain orange oil and xanthan gum. The caries remover comprising bromelain and limonene, comprising macrogol as a base and further comprising polyoxyethylene hydrogenated castor oil (60). The caries remover according to claim 1 or 2, which is a caries remover containing bromelain and limonene, contains gelled hydrocarbon as a base, and further contains sucrose fatty acid ester. The caries remover according to claim 1 or 2, which is a caries remover containing bromelain and limonene, contains gelled hydrocarbon as a base, and further contains sucrose fatty acid ester and hydroxypropylmethylcellulose.