JP2014530854A - Tooth film formulation - Google Patents

Abstract

The present invention relates to i. An acrylate / octylacrylamide copolymer, ii. One or more alkyl cellulose ethers, and iii. Novel dental film-forming compositions comprising a solvent and optionally further comprising a whitening material and / or an active reagent, and methods of use thereof are provided.

Description

(Field of Invention)
The present invention relates to novel film compositions that are applied to teeth to provide whitening or other benefits.

(Background of the Invention)
Most of the tooth whitening systems used today contain peroxides or other bleaching substances. Peroxide-based products have formulation problems due to the volatility and reactivity of hydrogen peroxide, and in many countries the peroxide concentration in tooth white products is strictly regulated.

  There is also a need for protecting teeth from bacteria and plaque formation and providing sustained delivery of active substances such as fluoride, antibacterial agents and remineralization reagents.

  Polymer delivery systems applied to teeth are generally not proven to be durable enough to remain on the teeth for the expected period of time. Teeth are physically worn by brushing and chewing. Furthermore, they are exposed to a wide range of temperatures and pH levels as a result of eating and drinking. Therefore, most polymers do not stay in the teeth for long periods under normal conditions. Furthermore, it is desirable that the polymer itself does not readily discolor or decolorize the teeth.

  There is an unmet need in the art for delivery systems that can provide teeth with whitening particles and other active ingredients, and that can protect teeth from plaque and biofilm for the expected period of time.

(Brief description of the invention)
We believe that formulations containing acrylate / octylacrylamide copolymers are suitable for dental applications, that the formulations are easy to apply, and that even when faced with brushing or acid loading It has been found that the object is more durable than other polymer systems. Thus, we have found that the formulation provides whitening particles and / or active agents to the teeth, and applies them to the teeth, to protect the teeth from coloration (stain), as well as to caries and gingivitis. It has been found to be a preferred vehicle for protecting teeth from the resulting biofilm and plaque formation.

In one embodiment, the present invention provides a dental film-forming composition comprising:
i. For example, an acrylate / octylacrylamide copolymer, such as 2-propenoic acid, 2-methyl-, 2-methylpropyl ester, in an amount of, for example, 5 wt% to 30 wt%, such as greater than 10 wt%, such as about 20 wt%. Polymers of 2-propenoic acid and N- (1,1,3,3-tetramethylbutyl) -2-propenamide) (eg, DERMACRYL79®);
ii. One or more alkyl cellulose ethers in an amount of, for example, 1% to 20% by weight, for example about 5% by weight;
iii. Orally acceptable solvents such as ethanol.
The formulation can be applied to provide a film that provides protection against stains and bacteria, and / or may optionally include one or more of the following materials: for example, titanium dioxide, zinc oxide, hydroxyapatite Or a whitening reagent comprising a combination thereof; one or more antibacterial agents such as triclosan; and / or one or more fluoride ion sources such as sodium monofluorophosphate; calcium sources such as calcium carbonate; basic amino acids such as free Form or salt form of arginine; or other active reagents.

  The present invention further comprises a method for whitening teeth and / or a method for protecting teeth against damage by stains or bacteria and / or a method for delivering active ingredients, which comprises applying a formulation of the present invention to the teeth. provide.

  Furthermore, the field of application of the present invention will become clear from the detailed description given below. The detailed description and specific examples, while indicating the preferred embodiment of the invention, are intended for purposes of illustration only and are not intended to limit the scope of the invention. Should be understood.

(Detailed description of the invention)
The following description of the preferred embodiment (s) is merely exemplary in nature and is not intended to limit the invention, its application or uses in any way.

  The “acrylate / octyl acrylamide copolymer” is selected from octyl acrylamide (eg N- (1,1,3,3-tetramethylbutyl) -2-propenamide) and acrylic acid, methacrylic acid and their simple esters. A copolymer with one or more monomers. In certain embodiments, the acrylate / octylacrylamide copolymer comprises 2-propenoic acid, 2-methyl-, 2-methylpropyl ester, 2-propenoic acid and N- (1,1,3,3-tetramethyl. Butyl) -2-propenamide (CAS129702-02-9), such as DERMACRYL® 79 (commercially available from National Starch or AkzoNobel).

  “Alkyl cellulose ether” means a lower alkyl ether of cellulose, for example ethyl cellulose, for example ethoxylation degree 45% to 50% and viscosity 3 to 70 mPa seconds (5% solution at 25 ° C. measured with Ubbelohde viscometer ) Ethylcellulose, such as the Ethocel® product line available from The Dow Chemical Company, such as Ethocel® E7, Ethocel® E22 or Ethocel® E50. The alkyl of the alkyl cellulose ether is optionally hydroxy substituted, such as hydroxypropyl cellulose.

  “Varnish” means typical varnish, eg, drying oil, resin, and thinner or solvent, and shellac and lacquer.

  “Orally acceptable” means safe at the concentration required for oral use.

Thus, the present invention in the first embodiment,
i. Acrylate / octylacrylamide copolymer;
ii. One or more alkyl cellulose ethers; and iii. solvent,
A dental film-forming composition (Composition 1) comprising:
For example,
1.1 An acrylate / octylacrylamide copolymer is 2-propenoic acid, 2-methyl-, 2-methylpropyl ester, 2-propenoic acid and N- (1,1,3,3-tetramethylbutyl) -2 -Composition 1 which is a polymer of propenamide;
1.2 Composition 1 or Composition 1.1, wherein the acrylate / octylacrylamide copolymer is present in an amount of 5% to 30% by weight;
1.3 Any of the preceding compositions wherein the acrylate / octyl acrylamide copolymer is present in an amount greater than 10% by weight;
1.4 Any of the preceding compositions wherein the acrylate / octylacrylamide copolymer is present in an amount of about 20% by weight;
1.5 Any of the preceding compositions wherein the alkyl cellulose ether is ethyl cellulose;
1.6 Any of the preceding compositions wherein the alkyl cellulose ether is a combination of ethyl cellulose and hydroxypropyl cellulose, such as hydroxypropyl cellulose;
1.7 Any of the preceding compositions comprising ethylcellulose and hydroxypropylcellulose in a ratio of 2: 1 to 30: 1, such as about 4: 1;
1.8 Any of the preceding compositions wherein the alkyl cellulose ether component is present in an amount of 1% to 20% by weight;
1.9 Any of the preceding compositions comprising ethylcellulose in an amount of 1% to 10%, such as an amount of 2% to 5%;
1.10 Any of the preceding compositions comprising hydroxypropylcellulose in an amount of 0.01% to 1%, such as an amount of about 0.25% or 0.5%;
1.11. Any of the preceding compositions comprising about 2% ethylcellulose and about 0.5% hydroxypropylcellulose;
1.12. Any of the preceding compositions wherein the orally acceptable solvent is ethanol;
1.13 any of the preceding compositions comprising a whitening substance;
1.14 any of the preceding compositions comprising an aqueous whitening material;
1.15 Any of the preceding compositions wherein the whitening material is selected from titanium dioxide, zinc oxide, hydroxylapatite and combinations thereof;
1.16 any of the preceding compositions comprising an effective amount of an antimicrobial agent, such as triclosan;
1.17 Any of the preceding compositions comprising a fluoride ion source, such as sodium monofluorophosphate;
1.18 Any of the preceding compositions comprising a calcium source, such as calcium carbonate;
1.19 any of the preceding compositions comprising a basic amino acid, such as arginine in free or salt form;
1.20 any of the preceding compositions in liquid form;
1.21 any of the preceding compositions in gel form;
1.22 Any of the preceding compositions free of burnish;
1.23 Any of the preceding compositions comprising the following ingredients on a weight basis:
Ethyl cellulose 1% -7%, for example 2% -5%,
Hydroxypropylcellulose 0.1% to 0.75%, such as about 0.25% to 0.5%,
Acrylate / octylacrylamide copolymer 10% to 30%, for example about 20%,
A sufficient amount of ethanol to dissolve the ingredients,
Water and, if desired, a sufficient amount of whitening material to give a white color when applied to the teeth.
2. In a further embodiment, the present invention provides a package comprising any of the above compositions and an applicator for applying the composition to a tooth.
3. In a further embodiment, the present invention provides a method of protecting teeth from stains or bacteria comprising applying the composition to the teeth.
4). In a further embodiment, the present invention provides the use of any of the above compositions in the manufacture of an oral care product that protects teeth from stains or bacteria.

  As used throughout this specification, a range is used as an abbreviation for each of the numerical values within that range. Any numerical value within the range can be selected as the upper and lower limits of the range. In addition, all citations cited herein are fully incorporated by reference herein in their entirety. In the event that there is a conflict between the definitions in the present disclosure and the definitions in the cited examples, the present disclosure shall control.

  Unless otherwise specified, all percentages and amounts given in this disclosure and throughout the specification refer to percentages by weight. The amounts shown are based on the active weight of the substance.

Ｅ７ − エチルセルロース（Ｅｔｈｏｃｅｌ（登録商標）Ｅ７（Ｄｏｗ））
ＨＰＣ − ヒドロキシプロピルセルロース
Ａ／Ｏ − アクリレート／オクチルアクリルアミド共重合体（ＤＥＲＭＡＣＲＹＬ（登録商標）７９）
ＥＰＯ − メタクリル酸ブチル−（２−ジメチルアミノエチル）メタクリレート−メタアクリル酸メチル共重合体
ＲＬ１００ − アンモニウムメタクリル酸塩共重合体 Example 1-Effect Comparison of Formulations Test formulations are prepared as follows:

E7-ethylcellulose (Ethocel® E7 (Dow))
HPC-hydroxypropylcellulose A / O-acrylate / octylacrylamide copolymer (DERMACRYL (registered trademark) 79)
EPO-butyl methacrylate- (2-dimethylaminoethyl) methacrylate-methyl methacrylate copolymer RL100-ammonium methacrylate copolymer

Percentage of coating removed with mechanical challenge and acid load:
The enamel block is stained (colored) by first exposing it to the peptide 20 μM peptide (DE62) and then staining with a 0.5% Red Iron Oxide suspension in 10 mM phosphate buffer. . The stained enamel blocks are each treated with 1 ml of formulation for 2 minutes and allowed to air dry. For application with a wet cotton swab (wet application), a styrofoam swab is moistened with water and used for a swipe test. For brushing load, a 1: 2 :: toothpaste: water slurry is prepared and used for brushing. This toothpaste is a commercial product toothpaste (COLGATE Max Fresh®). Brush each block for 15 seconds. For acid loading, the treated block is exposed to pH = 3.8 acid for 5 minutes and again brushed with a toothpaste for 15 seconds.

Percentage of coating removed by 5 hours saliva exposure at 37 ° C:
In order to simulate the condition in the oral cavity, each treated (coated) block is treated with 1 ml of cleaned whole saliva and incubated at 37 ° C. for 5 hours. After processing, each block is again tested with various load tests and the coating removal percentage is recorded. Thus, in the following table, the smaller the percent removed, the greater the durability and effectiveness of the coating.

  Each block is exposed to all three loads in turn. Only the formulation containing 20% acrylate / octylacrylamide copolymer (C) was not affected by brushing, acid and saliva, but the formulation containing 10% acrylate / octylacrylamide copolymer (B) was Similarly, almost the same performance was shown.

  Stain test: This test is designed to verify whether the coated surface attracts stain. Bovine enamel blocks are coated with the original solution and exposed to 40 ° C. black tea-stained stain (1: 2 ratio) for 30 minutes when dried. The white level is measured both before and after exposure to the stain solution.

  At 40 ° C., coatings A-F do not remain at high temperature conditions and the coating is completely removed without any mechanical force. According to EPO (D and E), 30% to 50% of the coating is peeled off after processing without any further mechanical force, and the remaining coating is duller, which means that the coating is black and white. It shows that the stain was adsorbed from the stain solution. Only prototypes B and C containing the acrylate / octylacrylamide copolymer remain at high temperature conditions and these prototypes do not further adsorb stain. Thus, the combination is useful for preventing stains.

また、分散剤としてのエチルセルロース／ヒドロキシプロピルセルロースを含む配合物は、他の配合物と比較して、良好な光沢および平滑な感覚を有することは注目される。 In addition, ethylcellulose and hydroxypropylcellulose act as dispersants, and in the case of ethylcellulose, act as additional film formers, and their presence probably increases the hydrophobicity of the film, thereby increasing the acrylate / octylacrylamide copolymer. Improves the stain protection effect of the combined formulation. As indicated above, according to Formulation A, ethylcellulose and hydroxypropylcellulose itself do not adsorb to the teeth and are therefore completely ineffective, hence this is a surprising synergy. The control for this experiment is a bare enamel block; a more negative L value indicates increased stain.

It is also noted that formulations containing ethylcellulose / hydroxypropylcellulose as a dispersant have better gloss and a smooth feel compared to other formulations.

Example 2-Stability Comparison of Formulations Drying time and stability are also evaluated. Stability is evaluated using optical centrifugation as a predictive model for physical stability. The formulation is injected into a small centrifuge tube. The sample is placed horizontally on a rotating plate and rotated / centrifuged at high speed (about 2400 rpm) for about 3 days. Light emitted from the light source passes through the cell, and the transmitted light is recorded by a detector. The percent transmitted light is profiled over time, and there is an established correlation between the degree of separation (indicated by increased light transmission) and shelf stability. A stability score of 3 or less is considered acceptable. Some of the formulations tested have stability that may correspond to shelf stability of about 6-12 months.

Formulations containing various amounts of dispersant are prepared as described in Tables 3a, 3b and 3c below. The unit is milliliter per 10 mL total volume:

Measure the drying time of the various formulations. Shorter drying times are desirable.

The stability, which measures the degree of relative separation of the components, is then evaluated in an optical centrifuge model to predict the stability of 3 months, 6 months and 1 year, as shown in Table 5. To do. The numbers in Table 5 reflect the degree of separation, with lower numbers indicating higher stability and 3 and lower indicating stability:

  Formulation 10 shows good stability, and Formulations 4, 6 and 9 also show good stability. Presumably, formulations showing a shorter drying time tend to have better stability because both parameters are related to the degree of dispersion.

Claims (12)

i. Acrylate / octylacrylamide copolymer,
ii. One or more alkyl cellulose ethers, and iii. solvent,
A dental film-forming composition comprising:   Acrylate / octylacrylamide copolymer is 2-propenoic acid, 2-methyl-, 2-methylpropyl ester, 2-propenoic acid and N- (1,1,3,3-tetramethylbutyl) -2-propene The composition of claim 1 which is an amide polymer.   The composition according to claim 1 or 2, wherein the acrylate / octylacrylamide copolymer is present in an amount of 5% to 30% by weight.   A composition according to any one of the preceding claims, wherein the acrylate / octylacrylamide copolymer is present in an amount of more than 10% by weight.   The composition according to any one of the preceding claims, wherein the one or more alkyl cellulose ethers comprise ethyl cellulose and hydroxypropyl cellulose.   6. The composition of claim 5, wherein the ratio of ethyl cellulose to hydroxypropyl cellulose is 2: 1 to 30: 1.   The composition according to any one of the preceding claims, wherein the orally acceptable solvent is ethanol.   A composition according to any preceding claim, further comprising a whitening substance.   9. The composition of claim 8, wherein the whitening material is selected from titanium dioxide, zinc oxide, hydroxylapatite and combinations thereof.   The composition according to any one of the preceding claims, comprising one or more antibacterial agents, fluoride ion sources, calcium sources or basic amino acids.   A package comprising the composition according to any one of claims 1 to 10 together with an applicator for applying the composition to a tooth.   A method for protecting a tooth from stains or bacteria comprising applying the composition according to any one of claims 1 to 10 to the tooth.