JP6444704B2 - Veterinary dental care composition - Google Patents

Description

  The present invention relates to a composition useful for softening or dissolving calculus of non-human animals, promoting calculus removal, or inhibiting calculus formation.

  In recent years, the prevalence of periodontal disease caused by dental plaque and calculus is increasing in pet animals in accordance with longer life and changes in dietary habits. Dental care for pet animals is a major concern for breeders. Conventionally, prevention or removal of plaque and tartar has been performed by feeding animals with hard food (such as cowhide). When hard food comes into contact with plaque or calculus in the animal's mouth, it is physically removed by scraping or crushing the calculus. However, such hard foods can effectively remove plaque and calculus where the dental plaque and calculus have the tip of the tooth, but are not effective in removing calculus present in the portion close to the gingiva. Complete removal of animal calculus usually requires surgery under general anesthesia. However, general anesthesia is high risk and is not particularly suitable for elderly animals without physical strength.

  On the other hand, a composition for removing calculus by softening or dissolving it has been proposed. Patent Document 1 discloses a calculus softening / dissolution that is unsaturated with respect to calculus components (hydroxyapatite, quaternary calcium phosphate, tertiary calcium phosphate or dicalcium phosphate) and supersaturated with fluorapatite and calcium fluoride. A composition is disclosed, which is believed to work to recalcify teeth with the fluorine component while dissolving tartar. Patent Document 2 discloses a calculus and / or caries part solubilizer containing as an active ingredient one or more substances selected from the group consisting of phosphoric acids, edetates, tartaric acid, malic acid, and citric acid. Is disclosed.

  The agents described in Patent Documents 1 and 2 are provided as those applicable to both human and non-human animals. In practice, however, the components of tartar differ between humans and non-human animals. The main component of calculus is calcium phosphate in humans, but it is known that dogs and horses contain calcium carbonate, and cats contain both carbonate and phosphate groups. On the other hand, tooth enamel is mainly composed of calcium phosphate (hydroxyapatite) in both human and non-human animals.

JP 09-143043 A JP 2005-139201 A

  The present invention provides a calculus softening or dissolution agent, a calculus removal accelerator or a calculus formation inhibitor for non-human animals, which can soften or dissolve the calculus while suppressing the dissolution of non-human animal tooth enamel as much as possible. It relates to the agent.

  The present inventors paid attention to the fact that the components of calculus differ between humans and non-human animals, and by using a composition that selectively dissolves calcium carbonate, the calculus can be reduced while suppressing damage to the teeth of non-human animals. The idea was that it could be removed selectively. As a result of many studies based on this idea, the inventors have succeeded in developing a composition capable of selectively softening or dissolving calculus of non-human animals.

That is, the present invention provides the following composition:
(A) Calcium ions 1 to 300 mM, and (B) Substance 7 to 300 mM having a pKa of 3 or more and less than 6.
Containing;
the pH is 3 or more and less than 6, and
0.63 x log ₁₀ [B] + 4.04 ≤ [log ₁₀ [Ca ²⁺ ] + [pH] x 1.1] ≤ 1.01 x log ₁₀ [B] + 5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition the concentration (mM) of the substance having a pKa of 3 or more and less than 6, provided that [log ₁₀ [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less.
A tartar softening or solubilizing agent for non-human animals is provided.

  The present invention also provides a calculus removal promoter for non-human animals comprising the above composition as an active ingredient.

  The present invention also provides a calculus formation inhibitor for non-human animals comprising the above composition as an active ingredient.

  The present invention also provides a method for softening or dissolving calculus, promoting calculus removal, or inhibiting calculus formation in a non-human animal, comprising feeding a non-human animal with a diet to which the above agent is added.

  The composition provided by the present invention can selectively soften or dissolve the calculus of the non-human animal, thereby promoting the removal of the calculus while suppressing as much as possible the damage to the teeth of the non-human animal, or The formation and accumulation of tartar can be suppressed.

Effect index of each test solution in Test 1: The citric acid concentration of each test solution is plotted on the horizontal axis (X), and the value of [log ₁₀ [Ca ²⁺ ] + [pH] × 1.1] is plotted on the vertical axis (Y). Graph. Effect index: ◆: 0.70 to 1.00, ●: 0.50 to less than 0.70, ○: 0.33 to less than 0.50, x: less than 0.33. Line (1): X = 7, Line (2): X = 300, Line (3): Y = 5, Line (4): Y = 7.2, Line (5): Y = 0.63 × log ₁₀ X + 4.04, straight line (6): Y = 1.01 × log ₁₀ X + 5.49. The tooth | gear before and after the liquid immersion in Test 2, and the photograph of the liquid after tooth immersion. The arrow represents the detached tartar.

The present invention provides a calculus softening or dissolution agent, a calculus removal promoter, or a calculus formation inhibitor for non-human animals. The calculus softening or dissolution agent, calculus removal promoter, or calculus formation inhibitor of the present invention has the following composition:
(A) Calcium ions 1 to 300 mM, and (B) Substance 7 to 300 mM having a pKa of 3 or more and less than 6.
Containing;
the pH is 3 or more and less than 6, and
0.63 x log ₁₀ [B] + 4.04 ≤ [log ₁₀ [Ca ²⁺ ] + [pH] x 1.1] ≤ 1.01 x log ₁₀ [B] + 5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition the concentration (mM) of the substance having a pKa of 3 or more and less than 6, provided that [log ₁₀ [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less.
Is the active ingredient.

Examples of the (A) calcium ion source contained in the composition of the present invention include inorganic calcium salts such as calcium chloride, calcium nitrate, calcium carbonate, calcium sulfate, calcium glycerophosphate, and calcium hydroxide; Organic calcium salts such as calcium acetate, calcium malonate, calcium citrate, calcium gluconate, calcium glycerate, calcium tartrate, calcium phytate; and calcium phosphate, Ca (HPO ₄ ) · 2H ₂ O (dicalcium phosphate; DCPD), Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O (octacalcium phosphate; OCP), Ca ₉ (PO ₄ ) ₆ (various) (amorphous calcium phosphate; ACP), Ca ₃ (PO ₄ ) ₂ (tri calcium Fosufe _{; TCP), Ca 10 (PO} 4) 6 (OH) 2 ( hydroxyapatite; HAP) calcium phosphate salts such as, and the like. One or more selected from the calcium salts listed above can be added to the composition of the present invention as a source of (A) calcium ions. Preferably a calcium phosphate salt is used. The concentration of (A) calcium ion in the composition of the present invention is 1 mM or more, preferably 3 mM or more, more preferably 5 mM or more, and 300 mM or less, preferably 200 mM or less, more preferably 100 mM or less, or preferably Is 1-300 mM, 1-200 mM, 1-100 mM, 3-300 mM, 3-200 mM, 3-100 mM, 5-300 mM, 5-200 mM, or 5-100 mM.

Examples of the substance (B) having a pKa of 3 or more and less than 6 contained in the composition of the present invention include lactic acid, acetic acid, ascorbic acid, oxalic acid, benzoic acid, fumaric acid, adipic acid, succinic acid, glucone Examples include acid, tartaric acid, malic acid, citric acid, glycolic acid, glutamic acid, aspartic acid, and salts thereof. One or more of these may be added to the composition of the present invention as a source of the (B) substance, and the type or combination of the (B) substance used is desired in the composition of the present invention. It can be appropriately selected according to the pH to be adjusted. Preferably citric acid and citrate are used. The concentration of the substance (B) in the composition of the present invention is 7 mM or more, preferably 8 mM or more, more preferably 10 mM or more, and 300 mM or less, preferably 200 mM or less, more preferably 150 mM or less, and even more preferably 100 mM or less. Or preferably 7-300 mM, 7-200 mM, 7-150 mM, 7-100 mM, 8-300 mM, 8-200 mM, 8-150 mM, 8-100 mM, 10-300 mM, 10-200 mM, 10-150 mM, Or 10-10
0 mM.

  The composition of the present invention may further contain (C) phosphate ions. Examples of the phosphate ion source include, in addition to the above-mentioned calcium phosphate salt, phosphoric acid, sodium phosphate, sodium hydrogen phosphate, potassium phosphate, potassium hydrogen phosphate, ammonium phosphate, ammonium hydrogen phosphate, phosphorus Examples thereof include inorganic phosphate compounds such as lithium phosphate, magnesium phosphate, zinc phosphate, and copper phosphate. These 1 type (s) or 2 or more types can be added to the composition of this invention as a supply source of (C) phosphate ion. Preferably, the above-mentioned calcium phosphate salt is used. The concentration of (C) phosphate ion in the composition of the present invention is 0.6 mM or more, preferably 1.8 mM or more, more preferably 3.0 mM or more, and 300 mM or less, preferably 200 mM or less, more preferably 100 mM or less. Alternatively, the concentration of (C) phosphate ion in the composition of the present invention is preferably 0.6 to 300 mM, 0.6 to 200 mM, 0.6 to 100 mM, 1.8 to 300 mM, 1.8 to 200 mM, It is 1.8-100 mM, 3.0-300 mM, 3.0-200 mM, or 3.0-100 mM.

  The composition of the present invention has a pH of 3 or more, preferably 3.5 or more, and less than pH 6, preferably 5.5 or less, more preferably 5 or less. Alternatively, the composition of the present invention has a pH of 3 to less than 6, preferably pH 3 to 5.5, more preferably pH 3 to 5, more preferably pH 3.5 to less than 6, still more preferably pH 3.5 to 5.5, The pH is preferably 3.5 to 5. The pH of the composition of the present invention can be adjusted by the addition of the above components (A) to (C), but is also adjusted by the addition of other pH adjusters such as pharmaceutically acceptable acids or alkalis. Can do.

Furthermore, in the composition of the present invention, (A) the concentration of calcium ions is adjusted to a specific range according to pH. If the calcium ion concentration in the composition of the present invention is too high, the dissolution ability of calcium carbonate, which is a calculus component, is reduced. On the other hand, if the concentration is too low, the dental enamel component (HAP) is dissolved together with the calculus component. This is not preferable. In addition, when the buffer capacity is too high, the composition of the present invention dissolves the dental enamel component (HAP) together with the tartar component, while when the buffer capacity is too low, the calcium carbonate which is the tartar component dissolves. The performance drops. Therefore, the composition of the present invention preferably satisfies the following conditions.
0.63 x log ₁₀ [B] + 4.04 ≤ [log ₁₀ [Ca ²⁺ ] + [pH] x 1.1] ≤ 1.01 x log ₁₀ [B] + 5.49
However, [log ₁₀ [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less, more preferably 5.3 or more and 7.2 or less.
In the above formula, [Ca ²⁺ ] represents the concentration (mM) of the above-mentioned (A) calcium ion in the composition of the present invention, [pH] represents the pH of the composition of the present invention, and [B] Represents the concentration (mM) of the substance in which the (B) pKa is 3 or more and less than 6 in the composition of the present invention.

  The composition of the present invention may further contain an active ingredient such as a bactericidal ingredient, bacteriolytic enzyme, surfactant, enamel remineralization ingredient (fluoride etc.) as an optional ingredient. Furthermore, the composition of the present invention contains a pharmaceutically acceptable carrier, for example, a gelling agent, a thickening agent, a shape retention agent, a buffering agent, an antiseptic, an osmotic pressure regulator, a dye, a fragrance and the like. Also good.

  The calculus softening or dissolution agent, calculus removal promoter, or calculus formation inhibitor for non-human animals containing the composition of the present invention as an active ingredient can be provided as a pharmaceutical or a quasi-drug. The pharmaceutical or quasi-drug can be used for softening or dissolving tartar in non-human animals, for promoting tartar removal, and for inhibiting tartar formation or accumulation. Therefore, it is useful for dental care in non-human animals and prevention of periodontal disease. The pharmaceutical and quasi-drug formulations include coatings and sprays that are applied to the oral calculus, and solid preparations that can spread or soften or dissolve the calculus when administered orally. Examples include oral preparations such as preparations and liquid preparations. What is necessary is just to determine suitably the administration interval and dose of the said pharmaceutical or quasi-drug depending on the species, age, sex, body weight, condition, etc. of the animal. For example, the dose for dogs and cats can be 0.01-100 g / kg body weight / day, preferably 0.04-50 g / kg body weight / day, as the amount of the composition of the present invention. The dosing interval can be, for example, three times a day, twice a day, once a day, once every two days, once every three days, twice a week, once a week, etc.

  The calculus softening or dissolution agent, calculus removal promoter, or calculus formation inhibitor for non-human animals containing the composition of the present invention as an active ingredient may also be used non-pharmaceutically or non-therapeutically. When used non-pharmaceutically or non-therapeutically, the above-mentioned agent of the present invention is a food / beverage product or dentifrice for non-human animals containing the composition of the present invention, or a food / beverage product or tooth brush for non-human animals Provided as a supplement to be added to the agent and orally administered to the non-human animal. The orally administered tartar softening or dissolving agent of the present invention spreads in the oral cavity and softens or dissolves tartar, promotes tartar removal, or forms tartar from ingredients of food or drink, Prevents ingredients from accumulating as tartar. The non-human animal food / beverage product, dentifrice or supplement containing the composition of the present invention promotes the removal of tartar, suppresses the formation of tartar, or reduces the accumulation of tartar on a daily basis. Maintain dental health.

  In the above food and drink and dentifrice, the composition of the present invention is preferably isolated from other components so as to be able to contact the calculus in the oral cavity while maintaining the composition. For example, the said food / beverage products and dentifrice can be the food / beverage products and dentifrice which the granular material and capsule containing the composition of this invention disperse | distributed to the whole. For example, the said food / beverage products and dentifrice can be the food / beverage products and dentifrice including the layer of the composition of this invention, and the filling containing the composition of this invention.

  Preferably, the above-mentioned supplement for food and drink and dentifrice is provided in the same package or in a separate package with the food and drink and dentifrice, and is added to the food and drink and dentifrice when applied to animals. The For example, the supplement is a jelly-like (or gel-like) composition, a granular composition, or an encapsulated composition that is topped on a daily diet, and spreads in the oral cavity as the animal ingests and chews.

  What is necessary is just to determine suitably the administration space | interval and dosage of the food / beverage products, the dentifrice, and the supplement containing the composition of the said invention according to the species, age, sex, body weight, state, etc. of an animal. For example, the dose for dogs and cats can be 0.02 to 100 g / kg body weight / day, preferably 0.04 to 50 g / kg body weight / day, as the amount of the composition of the present invention. The dosing interval can be, for example, every meal or three times a day, twice a day, once a day, once every two days, once every three days, twice a week, once a week, etc. . An animal given a food or drink containing the composition of the present invention may ingest the food or drink as a food, but may ingest other food or feed separately or simultaneously.

  Examples of the application target of the pharmaceutical or quasi-drug containing the composition of the present invention include non-human animals suffering from periodontal disease and non-human animals that require prevention of periodontal disease or removal of calculus. . Examples of the application target of foods and drinks, dentifrices and supplements containing the composition of the present invention include non-human animals for which suppression of calculus formation or reduction of calculus accumulation is desired in order to maintain dental health. Non-human animals to which the composition of the present invention is applied include non-human mammals, preferably dogs and cats.

  Preferable examples of the usage for applying the composition of the present invention to the non-human animal will be described below. First, a diet to which the composition of the present invention or the above-described agent of the present invention is added is prepared in advance. The type of diet may be selected according to the species, age, state, etc. of the non-human animal to be applied, and is not particularly limited. As a method for adding the composition or agent of the present invention to the diet, a feed, food or beverage containing the composition or agent of the present invention may be produced in the form described above, but daily supply such as a commercial product is possible. The composition or agent of the present invention may be topped or mixed with the feed, food or beverage to be used. When the non-human animal is ingested (for example, chewed or licked) with this diet or composition to which the present invention is added, the composition of the present invention comes into contact with the animal's teeth and softens or dissolves tartar. It exerts the effect of promoting removal or inhibiting calculus formation. The dose and administration interval of the composition of the present invention may be as described above, and can be changed according to the accumulation state of the animal's tartar.

  Therefore, the present invention also provides for non-human animal softening or dissolution of calculus, promotion of calculus removal, or inhibition of calculus formation, including feeding a non-human animal with a diet to which the composition or agent of the present invention is added. Or a method for preventing or improving periodontal disease in non-human animals. In the method, the composition or agent of the present invention is preferably a jelly-like (or gel-like) composition for topping on a diet, topped on the diet, and fed to the non-human animal. .

  As another exemplary embodiment of the present invention described above, the following is further disclosed herein.

<1> A composition comprising:
(A) calcium ion;
The calcium ion concentration is
Preferably it is 1 mM or more, more preferably 3 mM or more, more preferably 5 mM or more, and preferably 300 mM or less, more preferably 200 mM or less, even more preferably 100 mM or less, or preferably 1 to 300 mM, 1 to 200 mM. 1-100 mM, 3-300 mM, 3-200 mM, 3-100 mM, 5-300 mM, 5-200 mM, or 5-100 mM,
And (B) a substance having a pKa of 3 or more and less than 6, the concentration of the substance is
Preferably it is 7 mM or more, more preferably 8 mM or more, more preferably 10 mM or more, and preferably 300 mM or less, more preferably 200 mM or less, further preferably 150 mM or less, still more preferably 100 mM or less, or preferably 7 -300 mM, 7-200 mM, 7-150 mM, 7-100 mM, 8-300 mM, 8-200 mM, 8-150 mM, 8-100 mM, 10-300 mM, 10-200 mM, 10-150 mM, or 10-100 mM,
Containing;
The pH is 3 or more, preferably pH 3.5 or more, and less than pH 6, preferably pH 5.5 or less, more preferably pH 5 or less, or pH 3 to less than 6, preferably pH 3 to 5.5, more preferably Is pH 3-5, more preferably pH 3.5-6, more preferably pH 3.5-5.5, still more preferably pH 3.5-5;
and
0.63 x log ₁₀ [B] + 4.04 ≤ [log ₁₀ [Ca ²⁺ ] + [pH] x 1.1] ≤ 1.01 x log ₁₀ [B] + 5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition The concentration (mM)) of the substance having a pKa of 3 or more and less than 6; provided that [log ₁₀ [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less, preferably 5 .3 or more and 7.2 or less,
Composition.

<2> The composition according to <1>, preferably comprising:
(A) Calcium ion: 1 to 300 mM, and (B) Substance having a pKa of 3 or more and less than 6, 7 to 300 mM, 7 to 200 mM, 7 to 150 mM, 7 to 100 mM, 8 to 300 mM, 8 to 200 mM, 8 to 150 mM. 8-100 mM, 10-300 mM, 10-200 mM, 10-150 mM or 10-100 mM.

<3> The composition according to <1> or <2>, preferably (A) the concentration of calcium ions is 3 to 200 mM.

<4> Preferably, (A) <1> or <2> composition whose calcium ion concentration is 5 to 100 mM.

<5> The composition according to any one of <1> to <4>, wherein (B) the concentration of the substance having a pKa of 3 or more and less than 6 is 7 to 300 mM.

<6> Preferably, (B) The composition according to any one of <1> to <4>, wherein the concentration of the substance having a pKa of 3 or more and less than 6 is 8 to 200 mM.

<7> Preferably, (B) The composition according to any one of <1> to <4>, wherein the concentration of the substance having a pKa of 3 or more and less than 6 is 10 to 100 mM.

<8> Preferably from pH 3 to less than 6, more preferably from pH 3.5 to less than 6, more preferably from pH 3.5 to 5.5, still more preferably from pH 3.5 to 5, from <1> to <7> The composition of any one.

<9> The composition according to any one of <1> to <8>, preferably further comprising (C) a phosphate ion.

<10> The concentration of (C) phosphate ion is preferably 0.6 mM or more, more preferably 1.8 mM or more, further preferably 3.0 mM or more, and 300 mM or less, preferably 200 mM or less, more preferably 100 mM or less, or preferably 0.6 to 300 mM, 0.6 to 200 mM, 0.6 to 100 mM, 1.8 to 300 mM, 1.8 to 200 mM, 1.8 to 100 mM, 3.0 to 300 mM 3.0-200 mM, or 3.0-100 mM,
The composition according to <9>.

<11> A calculus softening or dissolution agent, a calculus removal accelerator, or a calculus formation inhibitor for a non-human animal, comprising the composition according to any one of the above items <1> to <10> as an active ingredient.

<12> Use of the composition according to any one of the above <1> to <10> for softening or dissolving tartar, promoting tartar removal, or inhibiting tartar formation in a non-human animal.

<13> The composition according to any one of the above <1> to <10>, for use in softening or dissolution of calculus in a non-human animal, promotion of calculus removal, or inhibition of calculus formation.

<14> Use of the composition according to any one of <1> to <10> for the manufacture of a calculus softening or dissolution agent, a calculus removal accelerator, or a calculus formation inhibitor for non-human animals.

<15> A method for softening or dissolving calculus of a non-human animal, a method for promoting calculus removal, or calculus formation, comprising administering the composition according to any one of <1> to <10> above to a non-human animal. Inhibition method.

<16> A preventive or ameliorating agent for periodontal disease for non-human animals, comprising the composition according to any one of <1> to <10> above as an active ingredient.

<17> The composition according to any one of the above <1> to <10>, which is used for preventing or improving periodontal disease in non-human animals.

<18> Use of the composition according to any one of the above <1> to <10> for the production of an agent for preventing or improving periodontal disease for non-human animals.

<19> A method for preventing or improving periodontal disease in a non-human animal, comprising administering the composition according to any one of <1> to <10> above to a non-human animal.

<20> In the above items <11> to <19>, preferably, the non-human animal is a dog or a cat.

<21> In the above <12> and <14>, preferably, the composition is used non-therapeutically.

  EXAMPLES Hereinafter, an Example is shown and this invention is demonstrated more concretely.

Test 1: Model calculus dissolution test (A) Calcium ions, (B) Citric acid as a substance having a pKa of 3 or more and less than 6, and (C) Phosphate ions at various concentrations to prepare test solutions with different pH did. (A) calcium ions, as (C) phosphate _{ions, CaCl 2, KH 2 PO 4} , hydroxyapatite, with either _{CaHPO 4, Ca 3 (PO 4} ) 2. The pH was adjusted by adding potassium hydroxide or hydrochloric acid. The composition of each test solution is shown in Tables 1-4. In addition, HAP in a table | surface means a hydroxyapatite. Sodium citrate in Table 4 was added to adjust the pH of the citric acid-containing test solution.

The test solution heated to 38 ° C. was dispensed in 200 μL aliquots into a 96-well microplate, and the absorbance (620 nm) of each well was measured while maintaining the temperature at 38 ° C. to obtain background absorbance.
Separately, 500 cc of ion-exchanged water heated to 38 ° C. is put in a 1 L beaker, and 0.1% by mass of hydroxyapatite (HAP) powder (model tooth) or calcium carbonate (CaCO ₃ ) powder (model tartar) while stirring with a stirrer. ) 0.4% by mass of each dispersion was added and dispersed. While maintaining a uniform dispersion state with a stirrer, the adjusted HAP dispersion or CaCO ₃ dispersion is quickly added to each well containing the test solution in the 96-well microplate using an 8-unit pipetter. Then, the absorbance (620 nm) of each well immediately after was measured as a reference value. Thereafter, stirring for 1 minute at 38 ° C. and 500 rpm on a plate shaker with a heating function → immediately measuring the absorbance (620 nm) of each well was repeated 5 times in the case of HAP dispersion, and CaCO ₃ dispersion was performed. In the case of liquid, it was performed once.
For each HAP dispersion and CaCO ₃ dispersion, a calculated value (Δ absorbance) was calculated by subtracting the corresponding background absorbance value from the last measured absorbance value.

As a reference value, the same test was performed by changing the test solution to ion-exchanged water, and Δ absorbance was calculated. For each test solution, the ratio of Δ absorbance (HAP absorbance ratio, CaCO ₃ ) when the Δ absorbance (reference value) of the dispersion in the corresponding ion-exchanged water is 1 for each of the HAP dispersion and CaCO ₃ dispersion. Absorbance ratio) was determined.
For each test solution, a value obtained by subtracting the value of the CaCO ₃ absorbance ratio from the value of the HAP absorbance ratio was determined and used as an effect index (−1 to +1). A test solution with a higher effect index is a more preferable test solution in which CaCO ₃ is more easily dissolved and HAP is more difficult to dissolve.

FIG. 1 shows the citric acid concentration (mM) on the horizontal axis (X), {log ₁₀ [Ca ²⁺ ] + [pH] × 1.1} ([Ca ²⁺ ] represents the calcium ion concentration (mM)). ) Is plotted on the vertical axis (Y) and the data in Tables 1 to 4 are plotted (except when the calcium ion concentration is 0). Each mark in FIG. 1 represents an effect index of each data, ◆: 0.70 to 1.00, ●: 0.50 to less than 0.70, ○: 0.33 to less than 0.50, X: represents less than 0.33. The marks in the column of the effect index in Tables 1 to 4 correspond to the marks in FIG. In the samples with * mark, the effect index could not be measured because the absorbance could not be measured due to the precipitation.
As shown in FIG. 1, {log ₁₀ [Ca ²⁺ ] + [pH] × 1.1} is 5.0 (straight line (3) in FIG. 1) or more and 0.63 × log ₁₀ [B] +4 .04 ([B] is the citric acid concentration (mM), straight line (5) in FIG. 1) or more, and 7.2 (straight line (4) in FIG. 1) or less and 1.01 × log ₁₀ [B] A test solution having a composition satisfying the condition of +5.49 (straight line (6) in FIG. 1) or less obtained a high effect index. Moreover, when the citric acid concentration of the test solution was in the range of 7 to 300 mM (between the straight lines (1) and (2) in FIG. 1), the solubility of CaCO ₃ was good and a high effect index was obtained.
That is, all the compositions shown in Tables 1 and 2 were included in the region surrounded by the straight lines (1) to (6) in FIG. 1, and the effect index was 0.33 or more. On the other hand, all the compositions shown in Tables 3 and 4 were outside the region surrounded by the straight lines (1) to (6) in FIG. 1, and the effect index was less than 0.33 or the effect index could not be measured.

  From the above results, the composition contained in the region surrounded by the straight lines (1) to (6) in FIG. 1 softens or dissolves tartar while suppressing the dissolution of the enamel of the teeth of non-human animals as much as possible. It has been found that this is a preferred composition that can be used.

Test 2: Dental calculus dissolution test The extracted teeth of dogs with calculus adhered were immersed in the liquids of Examples 1 and 2 and Comparative Example 1 and allowed to stand at room temperature for 1 week, and then the adhesion state of calculus was observed. The compositions of Examples 1-2 and Comparative Example 1 are described below.
Example 1: Ca ₃ (PO ₄ ) ₂ 0.10% by mass, citric acid · 1H ₂ O 0.20% by mass, pH = 3.82
Example 2: Ca ₃ (PO ₄ ) ₂ 0.30% by mass, citric acid · 1H ₂ O 1.00% by mass, pH = 3.32
Comparative Example 1: Purified water The results are shown in FIG. The teeth immersed in the liquids of Examples 1 and 2 had reduced tartar. Tartar peeled from the teeth was observed in the liquids of Examples 1 and 2 after immersion of the teeth. There was no change in the tartar of the teeth immersed in purified water.

Test 3: Tartar formation inhibition test with jelly-like composition for topping (1) Preparation of jelly-like composition While stirring 2,975 g of ion-exchanged water heated to 85 ° C. with sufficient stirring power, 1.50 g of fragrance, After dissolving 1.05 g of sweetener and 10.5 g of gellan gum-containing preparation (Gelup KS (F), manufactured by Saneigen FFI), 2.40 g of tricalcium phosphate is dispersed, and then xanthan gum / locust bean gum The preparation (gel-up SA-3C, manufactured by San-Eigen FFI) (3.00 g) was dissolved. After that, 6.60 g of citric acid monohydrate (crystal) was added and dissolved. 100 g of this was dispensed into bags (nylon poly G type, manufactured by Fukusuke Kogyo Co., Ltd.) heat-sealed so that the opening at the time of opening was 2 cm wide, and then allowed to stand at room temperature for gelation. The pH of the obtained gel was 3.8.

(2) Test procedure The test dogs (4 beagle dogs, body weight 11.7 kg to 13.5 kg at the start of the test) were divided into 2 groups of 2 animals, and a crossover test was conducted. Four courses were taken as one course, and two courses were conducted (early test and late test). During the test period, each individual was fed twice a day with a commercially available dog food (general nutrition food; manufactured by Nihon Hills Colgate Co., Ltd., Science Diet Adult Granules) in an amount that maintains the approximate body weight (first time: 9- 10 o'clock, second time: 16-17 o'clock). The bait plate had a rectangular shape of 15 cm × 7 cm on the inner bottom side, and the amount of salary was 110 to 135 g / head per salary.
In the first period test (Test 0 to 27 days), the first group is a group administered with the jelly-form composition of (1) (the second group is a control group), and in the latter period test (Test 28 to 55 days), the second group Were treated with the jelly composition of (1) (the first group was the control group). In the administration group, at each meal, the jelly-like composition was administered into the oral cavity of the individual by topping the jelly-like composition (1) (100 g / head) on the dog food and feeding with the food.

(3) Evaluation of calculus adhesion amount On the 0th day and the 28th day (= 0th day of the late period test), scaling was performed after evaluating the calculus adhesion amount of each individual under anesthesia. On the 28th day of the late test, the calculus adhesion amount was evaluated under anesthesia. The amount of calculus adhesion was evaluated for each of the left and right upper and lower jaw 6 teeth (3rd incisor, canine, 2nd premolar, 3rd premolar, 4th premolar, 1st postmolar), a total of 24 teeth did.
In the calculus adhesion amount evaluation, the plaque of each individual was wiped off with gauze under anesthesia, and then the calculus adhesion area and adhesion thickness were scored by visual evaluation according to Table 5. From the adhesion area score and the adhesion thickness score, the total score of tartar was calculated by the following formula. The results are shown in Table 6.

Claims (6)

The following composition:
(A) Calcium ions 1 to 300 mM, and (B) Substance 7 to 300 mM having a pKa of 3 or more and less than 6.
Containing;
the pH is 3 or more and less than 6, and
0.63 × log10 [B] +4.04 ≦ [log10 [Ca ²⁺ ] + [pH] × 1.1] ≦ 1.01 × log10 [B] +5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition the concentration (mM) of the substance having a pKa of 3 or more and less than 6, but [log10 [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less,
A tartar softening or dissolving agent for dogs or cats , comprising The following composition:
(A) Calcium ions 1 to 300 mM, and (B) Substance 7 to 300 mM having a pKa of 3 or more and less than 6.
Containing;
the pH is 3 or more and less than 6, and
0.63 × log10 [B] +4.04 ≦ [log10 [Ca ²⁺ ] + [pH] × 1.1] ≦ 1.01 × log10 [B] +5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition the concentration (mM) of the substance having a pKa of 3 or more and less than 6, but [log10 [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less,
A calculus removal promoter for dogs or cats , containing as an active ingredient. The following composition:
(A) Calcium ions 1 to 300 mM, and (B) Substance 7 to 300 mM having a pKa of 3 or more and less than 6.
Containing;
the pH is 3 or more and less than 6, and
0.63 × log10 [B] +4.04 ≦ [log10 [Ca ²⁺ ] + [pH] × 1.1] ≦ 1.01 × log10 [B] +5.49
( ^Wherein [Ca ²⁺ ]: concentration of (A) calcium ion in the composition (mM), [pH]: pH of the composition, [B]: (B) in the composition the concentration (mM) of the substance having a pKa of 3 or more and less than 6, but [log10 [Ca ²⁺ ] + [pH] × 1.1] is 5.0 or more and 7.2 or less,
A calculus formation inhibitor for dogs or cats , containing as an active ingredient.   The agent according to any one of claims 1 to 3, wherein the composition further contains a phosphate ion. A method for softening or dissolving tartar softening, promoting tartar removal, or inhibiting tartar formation in a dog or cat , comprising feeding the dog or cat with a diet to which the agent according to any one of claims 1 to 4 is added . The method according to claim 5 , wherein the agent is a jelly-like composition for topping.