CN104735996A - 口香糖 - Google Patents
口香糖 Download PDFInfo
- Publication number
- CN104735996A CN104735996A CN201380053431.8A CN201380053431A CN104735996A CN 104735996 A CN104735996 A CN 104735996A CN 201380053431 A CN201380053431 A CN 201380053431A CN 104735996 A CN104735996 A CN 104735996A
- Authority
- CN
- China
- Prior art keywords
- zinc
- chewing gum
- area
- chewing
- extract
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
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- 235000015218 chewing gum Nutrition 0.000 title claims abstract description 111
- 229940112822 chewing gum Drugs 0.000 title claims abstract description 107
- 239000011701 zinc Substances 0.000 claims abstract description 62
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims abstract description 59
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 59
- 239000000284 extract Substances 0.000 claims abstract description 41
- 206010006326 Breath odour Diseases 0.000 claims abstract description 31
- 208000032139 Halitosis Diseases 0.000 claims abstract description 31
- 208000024891 symptom Diseases 0.000 claims abstract description 11
- 239000000203 mixture Substances 0.000 claims description 49
- 239000011159 matrix material Substances 0.000 claims description 31
- 244000299492 Thespesia populnea Species 0.000 claims description 23
- 239000000419 plant extract Substances 0.000 claims description 20
- VVOAZFWZEDHOOU-UHFFFAOYSA-N magnolol Chemical compound OC1=CC=C(CC=C)C=C1C1=CC(CC=C)=CC=C1O VVOAZFWZEDHOOU-UHFFFAOYSA-N 0.000 claims description 18
- 150000003751 zinc Chemical class 0.000 claims description 17
- 230000001055 chewing effect Effects 0.000 claims description 16
- 210000000214 mouth Anatomy 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 15
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
- 150000005846 sugar alcohols Polymers 0.000 claims description 12
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 12
- 239000000945 filler Substances 0.000 claims description 11
- CANRESZKMUPMAE-UHFFFAOYSA-L Zinc lactate Chemical compound [Zn+2].CC(O)C([O-])=O.CC(O)C([O-])=O CANRESZKMUPMAE-UHFFFAOYSA-L 0.000 claims description 10
- 150000003464 sulfur compounds Chemical class 0.000 claims description 10
- 239000011576 zinc lactate Substances 0.000 claims description 10
- 235000000193 zinc lactate Nutrition 0.000 claims description 10
- 229940050168 zinc lactate Drugs 0.000 claims description 10
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 claims description 9
- 230000009467 reduction Effects 0.000 claims description 9
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 8
- 235000003599 food sweetener Nutrition 0.000 claims description 8
- 229940094952 green tea extract Drugs 0.000 claims description 8
- 235000020688 green tea extract Nutrition 0.000 claims description 8
- 239000003765 sweetening agent Substances 0.000 claims description 8
- 239000004246 zinc acetate Substances 0.000 claims description 8
- 235000013904 zinc acetate Nutrition 0.000 claims description 8
- WHMDKBIGKVEYHS-IYEMJOQQSA-L Zinc gluconate Chemical compound [Zn+2].OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O.OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O WHMDKBIGKVEYHS-IYEMJOQQSA-L 0.000 claims description 7
- 239000000975 dye Substances 0.000 claims description 7
- 239000000845 maltitol Substances 0.000 claims description 7
- 235000010449 maltitol Nutrition 0.000 claims description 7
- VQHSOMBJVWLPSR-WUJBLJFYSA-N maltitol Chemical compound OC[C@H](O)[C@@H](O)[C@@H]([C@H](O)CO)O[C@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O VQHSOMBJVWLPSR-WUJBLJFYSA-N 0.000 claims description 7
- 229940035436 maltitol Drugs 0.000 claims description 7
- 229960000314 zinc acetate Drugs 0.000 claims description 7
- 239000011670 zinc gluconate Substances 0.000 claims description 7
- 235000011478 zinc gluconate Nutrition 0.000 claims description 7
- 229960000306 zinc gluconate Drugs 0.000 claims description 7
- BYTORXDZJWWIKR-UHFFFAOYSA-N Hinokiol Natural products CC(C)c1cc2CCC3C(C)(CO)C(O)CCC3(C)c2cc1O BYTORXDZJWWIKR-UHFFFAOYSA-N 0.000 claims description 6
- FVYXIJYOAGAUQK-UHFFFAOYSA-N honokiol Chemical compound C1=C(CC=C)C(O)=CC=C1C1=CC(CC=C)=CC=C1O FVYXIJYOAGAUQK-UHFFFAOYSA-N 0.000 claims description 6
- -1 lysine-zn Chemical compound 0.000 claims description 6
- 239000011592 zinc chloride Substances 0.000 claims description 6
- 235000005074 zinc chloride Nutrition 0.000 claims description 6
- 229960001939 zinc chloride Drugs 0.000 claims description 6
- 239000002245 particle Substances 0.000 claims description 5
- 241000894007 species Species 0.000 claims description 5
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 4
- 238000000576 coating method Methods 0.000 claims description 4
- 239000003995 emulsifying agent Substances 0.000 claims description 4
- 229910052500 inorganic mineral Inorganic materials 0.000 claims description 4
- 235000010755 mineral Nutrition 0.000 claims description 4
- 239000011707 mineral Substances 0.000 claims description 4
- 239000011782 vitamin Substances 0.000 claims description 4
- 235000013343 vitamin Nutrition 0.000 claims description 4
- 229940088594 vitamin Drugs 0.000 claims description 4
- 229930003231 vitamin Natural products 0.000 claims description 4
- 150000003722 vitamin derivatives Chemical class 0.000 claims description 4
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 4
- 229960001763 zinc sulfate Drugs 0.000 claims description 4
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 4
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 244000139010 Spilanthes oleracea Species 0.000 claims description 3
- 235000007892 Spilanthes oleracea Nutrition 0.000 claims description 3
- 239000000796 flavoring agent Substances 0.000 claims description 3
- 235000019634 flavors Nutrition 0.000 claims description 3
- 239000000416 hydrocolloid Substances 0.000 claims description 3
- 229940041616 menthol Drugs 0.000 claims description 3
- 230000028327 secretion Effects 0.000 claims description 3
- 239000011885 synergistic combination Substances 0.000 claims description 3
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 2
- LQZFQLVBZRVDLJ-DKWTVANSSA-N (2s)-2-aminobutanedioic acid;zinc Chemical compound [Zn].OC(=O)[C@@H](N)CC(O)=O LQZFQLVBZRVDLJ-DKWTVANSSA-N 0.000 claims description 2
- VGTSYTYRRZZILH-UHFFFAOYSA-N 2,3-dihydroxypropanoic acid;zinc Chemical compound [Zn].OCC(O)C(O)=O VGTSYTYRRZZILH-UHFFFAOYSA-N 0.000 claims description 2
- CLWNPUARORRDFD-UHFFFAOYSA-N 2-hydroxybutanedioic acid;zinc Chemical compound [Zn].OC(=O)C(O)CC(O)=O CLWNPUARORRDFD-UHFFFAOYSA-N 0.000 claims description 2
- YSLIPUSJNFIFAB-UHFFFAOYSA-N 2-oxopyridine-1-carboxylic acid Chemical compound OC(=O)N1C=CC=CC1=O YSLIPUSJNFIFAB-UHFFFAOYSA-N 0.000 claims description 2
- 241000207199 Citrus Species 0.000 claims description 2
- 239000004471 Glycine Substances 0.000 claims description 2
- 235000014435 Mentha Nutrition 0.000 claims description 2
- 241001072983 Mentha Species 0.000 claims description 2
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 2
- 229960005070 ascorbic acid Drugs 0.000 claims description 2
- 235000010323 ascorbic acid Nutrition 0.000 claims description 2
- 239000011668 ascorbic acid Substances 0.000 claims description 2
- 239000003795 chemical substances by application Substances 0.000 claims description 2
- 235000020971 citrus fruits Nutrition 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims description 2
- MFGZXPGKKJMZIY-UHFFFAOYSA-N ethyl 5-amino-1-(4-sulfamoylphenyl)pyrazole-4-carboxylate Chemical compound NC1=C(C(=O)OCC)C=NN1C1=CC=C(S(N)(=O)=O)C=C1 MFGZXPGKKJMZIY-UHFFFAOYSA-N 0.000 claims description 2
- WGIWBXUNRXCYRA-UHFFFAOYSA-H trizinc;2-hydroxypropane-1,2,3-tricarboxylate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O WGIWBXUNRXCYRA-UHFFFAOYSA-H 0.000 claims description 2
- BIKXLKXABVUSMH-UHFFFAOYSA-N trizinc;diborate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]B([O-])[O-].[O-]B([O-])[O-] BIKXLKXABVUSMH-UHFFFAOYSA-N 0.000 claims description 2
- 239000011667 zinc carbonate Substances 0.000 claims description 2
- 235000004416 zinc carbonate Nutrition 0.000 claims description 2
- 229910000010 zinc carbonate Inorganic materials 0.000 claims description 2
- 239000011746 zinc citrate Substances 0.000 claims description 2
- 235000006076 zinc citrate Nutrition 0.000 claims description 2
- 229940068475 zinc citrate Drugs 0.000 claims description 2
- SRWMQSFFRFWREA-UHFFFAOYSA-M zinc formate Chemical compound [Zn+2].[O-]C=O SRWMQSFFRFWREA-UHFFFAOYSA-M 0.000 claims description 2
- 239000011787 zinc oxide Substances 0.000 claims description 2
- LRXTYHSAJDENHV-UHFFFAOYSA-H zinc phosphate Chemical compound [Zn+2].[Zn+2].[Zn+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O LRXTYHSAJDENHV-UHFFFAOYSA-H 0.000 claims description 2
- 229910000165 zinc phosphate Inorganic materials 0.000 claims description 2
- 229940032991 zinc picolinate Drugs 0.000 claims description 2
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 claims description 2
- 229940057977 zinc stearate Drugs 0.000 claims description 2
- VRGNUPCISFMPEM-ZVGUSBNCSA-L zinc;(2r,3r)-2,3-dihydroxybutanedioate Chemical compound [Zn+2].[O-]C(=O)[C@H](O)[C@@H](O)C([O-])=O VRGNUPCISFMPEM-ZVGUSBNCSA-L 0.000 claims description 2
- LPEBYPDZMWMCLZ-CVBJKYQLSA-L zinc;(z)-octadec-9-enoate Chemical compound [Zn+2].CCCCCCCC\C=C/CCCCCCCC([O-])=O.CCCCCCCC\C=C/CCCCCCCC([O-])=O LPEBYPDZMWMCLZ-CVBJKYQLSA-L 0.000 claims description 2
- WDHVIZKSFZNHJB-UHFFFAOYSA-L zinc;butanoate Chemical compound [Zn+2].CCCC([O-])=O.CCCC([O-])=O WDHVIZKSFZNHJB-UHFFFAOYSA-L 0.000 claims description 2
- ZPEJZWGMHAKWNL-UHFFFAOYSA-L zinc;oxalate Chemical compound [Zn+2].[O-]C(=O)C([O-])=O ZPEJZWGMHAKWNL-UHFFFAOYSA-L 0.000 claims description 2
- XDWXRAYGALQIFG-UHFFFAOYSA-L zinc;propanoate Chemical compound [Zn+2].CCC([O-])=O.CCC([O-])=O XDWXRAYGALQIFG-UHFFFAOYSA-L 0.000 claims description 2
- NHVUUBRKFZWXRN-UHFFFAOYSA-L zinc;pyridine-2-carboxylate Chemical compound C=1C=CC=NC=1C(=O)O[Zn]OC(=O)C1=CC=CC=N1 NHVUUBRKFZWXRN-UHFFFAOYSA-L 0.000 claims description 2
- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 claims 2
- ADRVNXBAWSRFAJ-UHFFFAOYSA-N catechin Natural products OC1Cc2cc(O)cc(O)c2OC1c3ccc(O)c(O)c3 ADRVNXBAWSRFAJ-UHFFFAOYSA-N 0.000 claims 2
- 235000005487 catechin Nutrition 0.000 claims 2
- 235000015111 chews Nutrition 0.000 claims 2
- 229950001002 cianidanol Drugs 0.000 claims 2
- 239000000546 pharmaceutical excipient Substances 0.000 claims 2
- 238000005303 weighing Methods 0.000 claims 2
- 150000008442 polyphenolic compounds Chemical class 0.000 abstract 1
- 235000013824 polyphenols Nutrition 0.000 abstract 1
- 230000002195 synergetic effect Effects 0.000 abstract 1
- 235000013311 vegetables Nutrition 0.000 abstract 1
- 230000000694 effects Effects 0.000 description 17
- 238000009472 formulation Methods 0.000 description 14
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- 239000001785 acacia senegal l. willd gum Substances 0.000 description 10
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- ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 1
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- 238000001727 in vivo Methods 0.000 description 1
- 230000000977 initiatory effect Effects 0.000 description 1
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- NFLGAXVYCFJBMK-UHFFFAOYSA-N isomenthone Natural products CC(C)C1CCC(C)CC1=O NFLGAXVYCFJBMK-UHFFFAOYSA-N 0.000 description 1
- 235000010355 mannitol Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 150000002729 menthone derivatives Chemical class 0.000 description 1
- 229910021645 metal ion Inorganic materials 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 239000008368 mint flavor Substances 0.000 description 1
- 235000019426 modified starch Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 235000015145 nougat Nutrition 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- CFJYNSNXFXLKNS-UHFFFAOYSA-N p-menthane Chemical compound CC(C)C1CCC(C)CC1 CFJYNSNXFXLKNS-UHFFFAOYSA-N 0.000 description 1
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- 239000000049 pigment Substances 0.000 description 1
- 239000004014 plasticizer Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 210000003296 saliva Anatomy 0.000 description 1
- 230000001953 sensory effect Effects 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BGRJTUBHPOOWDU-UHFFFAOYSA-N sulpiride Chemical compound CCN1CCCC1CNC(=O)C1=CC(S(N)(=O)=O)=CC=C1OC BGRJTUBHPOOWDU-UHFFFAOYSA-N 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- YZYKBQUWMPUVEN-UHFFFAOYSA-N zafuleptine Chemical compound OC(=O)CCCCCC(C(C)C)NCC1=CC=C(F)C=C1 YZYKBQUWMPUVEN-UHFFFAOYSA-N 0.000 description 1
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Abstract
本发明涉及口香糖,其包含锌和含多酚类的植物提取物的协同组合。所述口香糖可用于治疗口臭的症状。
Description
本发明涉及口香糖(chewing gums)。
现有技术
口臭是限制患者的社会生活的状况。据估计15%至40%的人口患有中等口臭(Rosing CK等人,Braz Oral Res 2011;25(5):466-71)。口臭通常由于存在挥发性硫化合物(VSC)而引起(Kleinberg I等人,Crit Rev Oral Biol.Med.1990;1(4):247-59)。所述化合物由口腔细菌分解代谢蛋白质而产生(DeBoever EH等人,J Am.Dent.Assoc 1995;126(10):1384-93)。鼻子可以将非常低浓度的VSC感知为令人不快的气味;在临床实践中认为在呼出的空气中75ppb(十亿分率)的VSC为中等口臭级别的最小阈值(van den Broek AM.等人,J Dent.2007;35:627-635)。
一些食物诸如大蒜和抱子甘蓝可以增加口臭(Tangerman A,.Halitosisin medicine:a review.Int.Dent J.2002;52增刊3:201-206)。此外,在一天的开始可能存在“晨起气息(morning breath)”,其主要由夜间生成的唾液的滞留引起的(Rosenberg M.J.Am.Dent.Assoc.1996;127:475-482)。大多数研究和专利发明集中于在每天特定时间(早晨)或在食用特定的食物后(诸如基于大蒜或甲硫氨酸的漱口剂)的口臭原因的抗菌治疗。
一些植物提取物由于一些针对口臭的特性被使用和描述;例如,可以在市场上找到含植物提取物的波状无糖软锭剂(pastilles)形式的包衣产品(含0.36%生咖啡豆和0.36%牛蒡的Hali ControlTM)。
已知含绿茶提取物的糖果和口香糖减少由基于大蒜的漱口剂产生的口臭(H.Yasuda,等人,Nippon Shishubyo Gakkai Kaishi,37,141,1995)。还已知含木兰树皮(Magnolia bark)提取物(MBE)的口香糖和片剂减少一些被认为是口臭的原因的细菌的唾液浓度(Greenberg M等人,J.Agric.Food Chem.2007;55(23):9465-9)。然而,用于针对非人为产生的口臭的症状的和使用所述植物提取物与锌盐的协同配制物的口香糖是未知的。
已经出版了关于基于锌盐的漱口剂减少用半胱氨酸(一种含硫氨基酸)漱口后人为产生的挥发性硫化合物的能力的论文。在所述论文中,锌的有效量(作为乙酸锌二水合物施用)范围为最小3mg至最大30mg(Young,A等人,(2003).Eur.J.Oral Sci.111(5):400-404).
含6.8mg各种盐形式的Zn的咀嚼片的一项研究得出结论:对由半胱氨酸漱口剂人为生成的VSC的作用不依赖于盐的溶解度常数(Young,A.,G.Jonski等人(2002),Eur.J.Oral Sci.110(1):31-34)。
最后,一项对11名志愿者进行的体内研究发现含2mg或0.5mg乙酸锌的口香糖分别使VSC减少45%和16%,与之相对照在咀嚼安慰剂口香糖后使VSC减少14%。在实践中,当使用0.5mg锌时,其作用与安慰剂的作用没有区别(Waler SM.Acta Odontol.Scand.1997;55(3):198-200)。
在一些专利中已经阐述了锌或植物提取物与具有抗口臭功能的其他成分的组合。它们涉及将所述混合物掺入口香糖中。
EP1998736公开了木兰树皮提取物和具有抗菌功能的精油的组合。
EP2046274公开了木兰树皮提取物和一些精油中天然包含的矫味化合物(特别是薄荷酮和异薄荷酮)的组合。据报道所述组合在减少由食用引起口臭的食品引起的口臭中特别有效。
EP1901704和EP1957169公开了木兰树皮提取物和表面活性剂的组合。
WO 02091848公开了与其他口腔卫生成分诸如木糖醇(抗-斑)和锌(抗-口臭)组合的草本提取物(包括绿茶提取物和木兰树皮提取物)的应用。然而,没有阐述植物提取物和锌的同时应用的最佳量。分别处理两种功能成分。事实上,植物提取物的目的是对抗口臭,而其他功能成分(口腔护理活性物质)的目的是提供口腔卫生领域的进一步的益处。
据报道草本提取物通过抗菌作用发挥其作用,但没有报道其对VSC的作用。
EP1387662公开了与多磷酸盐类和任选的MBE组合的两种不同的金属离子的用途。EP1843731还公开了与多磷酸盐类组合的MBE的用途,但其具有抗牙垢功能。
WO2006/079343公开了含锌盐和绿茶提取物的片剂形式的口香糖。
WO2007/067340报道了木兰(magnolia)提取物和任选的锌在口香糖中的用途。
KR2004/0019145报道了含锌盐和绿茶的漱口剂。其中没有关于MBE和锌在口香糖中的协同的组合的教导,尤其是没有关于能在患有真口臭(real halitosis)(即不是由含硫酸化氨基酸或大蒜的漱口剂引起的且与每天的特定时间(早晨)无关的口臭)的患者单独使用口香糖后保证长效的症状治疗的最佳剂量的教导。
发明描述
现已发现能够制备由至少一个具有胶基(gum base)的第一区域和没有胶基的完全水溶性的第二区域组成的口香糖,其包含有效量的选自木兰树皮(magnolia bark)提取物、绿茶提取物及其组合的植物提取物与有效量的锌离子(其至少部分包含在完全水溶性的微粒中)的协同组合。
本发明允许使用比文献中所教导的更低的量的锌。这产生感官优势(因为锌具有显著的涩味(astringent)能力),其能改善治疗的顺应性以及提供经济益处。
本发明可以有利地用于治疗口臭的症状,即减少呼出气体中的挥发性硫化合物(VSC)。换言之,适于在一定场合消费的单份口香糖产生上文提及的作用。
“单份(Single portion)口香糖”意指单个(piece)口香糖或可以同时消费的多个。单个口香糖可以选自以下形式和重量:重1g至3g的棒(stick)、重1g至4g的丸(pellet)、具有填充物的重1g至5g的丸、具有液体填充物的重1g至9g的泡泡糖或重1.5g至9g的多层棒。可以同时消费以形成单份的多个可以选自前述形式;然而,如果多个组合来形成单份,则单个的重量优选低于3g、甚至更优选低于2.5g,且在实施方案的一些形式中,低于1g。在本发明的实施方案中,无糖口香糖的应用是特别有利的。在口香糖的组合物中的可发酵糖的不存在防止口香糖为与VSC产生相关的微生物提供可发酵底物。同时,咀嚼增加唾液流量,其通过其清洁作用产生减少VSC的第一种作用。
口香糖包含矫味剂和添加剂,诸如甜味剂、酸化剂、增稠剂、湿润剂、乳化剂、抗氧化剂、稳定剂和包衣剂。
特别地,其中所述第一区域构成核心且所述完全水溶性的第二区域构成至少部分覆盖第一区域的包衣的口香糖是优选的。所述形式还称为丸(pellet)。
口香糖可以制备为多种形式,诸如垫子(cushion)、球、立方体和圆盘形状。
得到含胶基的根据本发明的口香糖的第一区域的方法是已知的。
含胶基的根据本发明的口香糖的第一区域的成分可以选自胶基(gumbase)、甜味剂诸如糖、多元醇、强甜味剂(intensive sweetener)、添加剂诸如染料、酸化剂、乳化剂、矫味剂(固体或液体形式)、湿润剂、工艺辅助剂诸如乳化剂或增塑剂、药理学活性成分、植物提取物、功能成分诸如维生素或矿物盐和染料。
如果本发明的实施方案的形式为丸形式的口香糖,则第一区域称为核心,且完全水溶性的第二区域称为包衣。
两种主要包衣类型为为硬和软包衣。
在硬包衣情况下,将核心放入包衣锅中,其中,一旦进行旋转,它们历经重复的浆体(syrup)-喷雾和干燥循环。在这些阶段中的一些阶段可以施加粉末。
浆体由糖或多元醇、水、粘合剂和任选的色素、强甜味剂和矫味剂的混合物构成。
多元醇用于包衣无糖口香糖。最常用的多元醇包括山梨醇、Isomalt、麦芽糖醇和木糖醇。
优选的粘合剂为水胶体,诸如阿拉伯胶、明胶、淀粉包括改性淀粉、及其混合物。
所述粉末可以简单地由研磨至非常细的颗粒的结晶的多元醇组成或者由多元醇与粘合剂的混合物诸如木糖醇与阿拉伯胶的混合物、甘露醇和阿拉伯胶的混合物或麦芽糖醇和阿拉伯胶的混合物组成。
包衣可以构成第二个完全水溶性区域。特别有利的是将本发明的植物提取物引入所述第二区域中。在实施方案的其他形式中,所述第二区域不包含如下文阐述的包衣。
在实施方案中的一些形式中,植物提取物包含在口香糖的第一区域中。
由麦芽糖醇或吡喃葡糖基-甘露醇和吡喃葡糖基-山梨醇的混合物(其占包衣的干重量的超过70%)组成的包衣是特别有利的。
在本发明的实施方案的一些形式中,第一区域可以包含至少一种填充物,其可以是固体,诸如硬糖、太妃糖、巧克力、杏仁糖或软糖料(fondant),或者可由含木糖醇或其他结晶的多元醇或结晶的右旋糖的颗粒物质组成。或者,所述填充物可采取液体形式,诸如浆体。通过实例描述的各形式的组合均是可能的。填充物可以包含一种或多种多元醇、添加剂、维生素、矿物盐包括锌盐、植物提取物包括绿茶和木兰树皮提取物、染料、酸化剂和矫味剂。
通常在挤压阶段期间将所述填充物引入包含胶基的第一区域中。
根据核心和填充物质的类型和单个口香糖的形状,填充物可完全掺入单个口香糖内或从口香糖一侧或多侧的外部可见。
作为丸形状的替代方案,可以将根据本发明的口香糖进行如下配制:使得所述第一区域和所述第二区域以重叠的、交替的层排列。用于所述特定构型的方法和配制物是已知的(US5437879)。
不论根据本发明的口香糖的实施方案的形式,优选的矫味剂是来自以下种属的那些:薄荷属、柑桔属、千日菊属,以及薄荷醇、具有清新口气和唾液分泌刺激剂功能的人工和天然矫味剂及其组合。源自薄荷(薄荷、留兰香等)和柑桔类水果(橙、柠檬、葡萄柚、酸橙等)的各物种的矫味剂、具有冷却剂功能的人造或天然矫味剂与冷却和清洁的感觉相关,且它们的令人愉快气味可以有效掩蔽口臭的感觉,由此实现传入感觉器可感觉的口臭症状减少的作用。
具有冷却剂功能的矫味剂通常为薄荷醇酯类诸如乳酸薄荷酯、琥珀酸薄荷酯和戊二酸薄荷酯;或酰胺类诸如N-乙基-对-薄荷烷-3-甲酰胺、2-异丙基-N,2,3-三甲基丁酰胺、3-(对-薄荷烷-3-甲酰氨基)-乙酸乙酯、N-对-苯-乙腈薄荷烷甲酰胺和N-(2-(吡啶-2-基)乙基)-3-对-薄荷烷-3-甲酰胺,但还可有其他化合物诸如异蒲勒醇(isopulegol)和(-)-薄荷氧基丙-1,2-二醇(即(-)-menthoxypropan-1,2-diol)。
具有刺激唾液分泌特性的矫味化合物诸如千日菊素(spilanthol)从千日菊属得到,最近已经向其添加了其他具有催涎特性的化合物诸如墙草碱(pellitorine)和山椒素(sanshool)。
在口香糖中包含离子形式的锌。此后,“锌”因此是指离子形式的。
特别有利的是在含胶基的第一区域中包含锌。包含在具有胶基的区域导致缓慢释放,这使得本发明的口香糖具有长效的功效。
锌至少部分上包含在完全水溶性的微粒中。所述完全水溶性的微粒不包含胶基制备中使用的聚合物。优选地,所述微粒包含一种或多种单独的或混合在一起的多元醇、水胶体、矫味剂、染料、甜味剂和其他添加剂。在实施方案的一个优选的形式中,微粒包含多于80%的山梨醇、少于2%的阿拉伯胶和多于1%的锌盐。“微粒”意指口香糖制备之前制备的具有小于1000μm的平均粒度的颗粒物质。特别地,优选至少90%的颗粒处于800μm至300μm之间的粒度。尽管可以将微粒引入具有胶基的部分或完全水溶性区域,但它们优选包含在具有胶基的区域。
当离子形式的锌的含量范围为0.0005%至0.05%重量,且植物提取物范围为0.02%至2%(成品的百分比)时,植物提取物和锌的协同作用更有效。
如果单份口香糖包含范围为0.012mg至1.2mg的锌离子和0.5mg至50mg的木兰树皮提取物,单份口香糖特别有效。作为木兰提取物的替代项,可以单独地或与木兰树皮提取物混合地使用绿茶提取物。
根据本发明的口香糖优选由至少一个具有胶基的区域和一个完全水溶性的没有胶基的区域组成。所述具有胶基的区域包含成品的0.005%至0.04%的锌离子,且没有胶基的区域包含范围为成品的0.07%至0.5%的木兰树皮提取物。
锌可以完全或部分地由前述的微粒携带。优选至少10%、甚至更优选至少20%的锌由前述的微粒携带,剩余的锌由具有胶基的区域直接包含的盐携带。
为了以离子形式携带锌,锌离子优选作为选自以下的盐存在:氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌、丁酸锌、甘油酸锌、羟乙酸锌、甲酸锌、乳酸锌、吡啶甲酸锌、丙酸锌、水杨酸锌、酒石酸锌、硫酸锌、抗坏血酸锌、双甘氨酸锌(bisglycinate)、赖氨酸锌、苹果酸锌、单-L-甲硫氨酸硫酸锌、吡酮酸锌(zinc pidolate)及其混合物。
特别优选乙酸锌、乳酸锌和葡萄糖酸锌及其混合物。
对于作为盐存在的锌离子,优选选自特征为在25℃中性pH时水-溶解度超过0.5g/100g的那些。因此它们是水溶性的盐,其可以有利地包含在微粒中,而所述微粒可以包含在具有胶基的区域中。
在本发明的一些实施方案中,口香糖包含另外的选自油酸锌、硬脂酸锌、柠檬酸锌、磷酸锌、碳酸锌、硼酸锌、草酸锌、天冬氨酸锌、氧化锌及其混合物的锌盐。
单份口香糖优选包含提供0.1至10mg锌的量的所述另外的锌盐。
在实施方案的一个优选的形式中,加入微粒中的锌盐和没有加入微粒中的锌盐是相同的。
在实施方案的一个备选的形式中,加入微粒中的锌盐与没有加入微粒中的锌盐是不同的。
与缺乏所述功能成分的口香糖相比以及与仅含两种功能成分之一的口香糖相比,根据本发明的口香糖更加减少挥发性硫化合物的口腔含量。在咀嚼后和随时间推移作用更大,如下文将证实的。
木兰树皮提取物是特别优选的。
木兰树皮提取物包含两种被认为是其活性成分的新木脂素,即厚朴酚(magnolol)及和厚朴酚(honokiol)。源自中国不同区域的传统提取物的分析证实厚朴酚浓度范围为最低0.005%至最高9.2%,而和厚朴酚浓度范围为最低0.008%至最高9.7%。两者的总和一直低于20%(Jiang,Y.,等人,Phytochem.Anal,2011,DOI 10.1002/pca.1369)。
所述两种新木脂素提取自根据所述方法制备的树皮(Pharmacopoeia ofthe PRC,(英语版),1988,People’s Medical Publishing House,北京,CortexMagnoliae Officinalis,第23-24页)。提取可以使用有机溶剂进行,或者最近使用超临界二氧化碳进行。
通过在超临界二氧化碳中提取、随后在乙醇中结晶得到的提取物是优选的。
优选使用厚朴酚含量范围为80%至88%、且和厚朴酚含量范围为8%至18%的提取物,其中两种新木脂素的总和优选超过85%且甚至更优选超过95%。
木兰树皮提取物可以从多种属于木兰属的植物包括和厚朴(Magnoliaobovata)以及厚朴(Magnolia officinalis)获得,且树皮可以源自植物的枝、干和根。优选使用得自亚种凹叶厚朴(Magnolia officinalis Rehder spp.Biloba.)的提取物。所述提取物优选得自树干皮。
木兰树皮提取物存在于无糖口香糖丸的包衣中且锌存在核心中。木兰树皮提取物优选以范围为0.5mg至50mg/单份口香糖且甚至更优选1至5mg/单份的量存在。将锌至少部分地引入如上文所述的含多于80%山梨醇和少于2%阿拉伯胶的微粒中,且单份口香糖优选包含0.012mg至1.2mg的锌、甚至更优选0.05至0.5mg的锌。含山梨醇的微粒中的锌浓度范围优选为0.06%至6%、甚至更优选0.5%至3%(微粒重量的百分比)。
微粒可以包含可食用的添加剂诸如染料、增稠剂、酸化剂、甜味剂、矫味剂、维生素和其他矿物盐。
刚描述的根据优选的形式制备的单份口香糖呈现出令人惊讶的减少具有临床口臭的人呼出的空气中的挥发性硫化合物的能力,且因此可以用于治疗口臭的症状。
事实上,在刚使用口香糖前呼出的气体中具有75ppb的最小VSC值的消费者中,与咀嚼前的值相比,单份口香糖咀嚼10分钟使呼出气体中挥发性硫化合物的平均浓度在咀嚼后最少降低40%。
此外,被呼出气体中具有75ppb的最小VSC值的消费者咀嚼10分钟的单份口香糖在咀嚼开始后1小时使呼出气体中的挥发性硫化合物的平均浓度降低至少15%。
使用市场上容易得到的OralChroma便携式气相色谱仪(OralChromaTM,Abilit公司,大阪,日本)测量VSC。
将没有锌、木兰或两者的口香糖配制物(参比配制物A、B和C)与含锌及木兰提取物两者的本发明配制物(配制物D、F和E)比较。配制物的组成在其他方面是相同的。特别地,使用丸形式的口香糖,其中将锌引入核心中的微粒中(第一区域),并将木兰树皮提取物引入包衣中(第二区域)。锌和木兰树皮提取物的量描述在表1中。
在10名具有75ppb的最小VSC水平(无论一天的时段,且没有用氨基酸或特定食品刺激VSC生成)的志愿者中评价挥发性硫化合物。在咀嚼前、刚咀嚼单份后(10分钟)和1小时后通过描述的方法进行评价。表1显示与起始情况相比的VSC的%降低。在咀嚼的末尾,志愿者进行口香糖的感觉评估。
类似地,在实施方案的一个优选的形式(配制物G)中评价降低VSC的能力,在配制物G中至少15%的锌(为总锌的百分比)被引入如上文描述的含多于80%山梨醇和少于2%阿拉伯胶的微粒中,且优选地,单份口香糖包含0.012mg至1.2mg的锌、甚至更优选0.05至0.5mg的锌。将微粒携带的锌作为选自以下盐的离子引入:氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌及其混合物。在口香糖丸的情况中,剩余部分(85%以下)的锌(为总锌的百分比)被直接引入含胶基的区域或核心的一种或多种氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌及其混合物携带。
所述数据证明口香糖A(参比)具有一定的降低口腔VSC的作用,尤其是在咀嚼后,但是该作用在1小时后大大降低。该作用可能是由于刺激唾液分泌,后者与对牙齿的机械摩擦作用一起洗掉引起口臭的细菌。所述仅含锌的参比口香糖改善了口腔VSC的降低,但主要是在长期的情况下。所述仅含木兰树皮提取物的参比口香糖在刚咀嚼后更有效,但在1小时后与不含木兰和锌的口香糖表现类似。
具有锌和木兰树皮提取物的协同组合的口香糖(D、E、F和G)在10分钟的咀嚼后立即和在1小时后均显著降低口腔VSC的百分比。在这两个时间点以及在全部四个配制物(D、E、F和G)中,所述降低均超过由不含锌和MBE的口香糖引起的降低和仅包含这两种功能成分之一的两种口香糖B和C引起的降低,这表明在刚咀嚼后以及在长期情况(参见1小时后的数据)获得协同作用。
通过进一步证明本发明的含锌和木兰的配制物的协同作用,可以计算协同作用百分比。其可以认为是由所述口香糖引起的超过仅包含两种功能成分之一的口香糖的VSC-降低作用之和的VSC的百分比降低,扣减不含任何功能成分的口香糖的作用。每当添加口香糖(不论本发明还是参比)的作用,特别重要的是扣除平常(plain)口香糖的作用(表1中的口香糖A),这类似于有背景噪音的处理过程。所述协同作用报告于表2中。高于0的数值表明了本发明配制物中锌和植物提取物的组合的协同作用。
高于配制物D和F中所使用的剂量将在配制物的气味方面产生令人不愉快的变化(涩味、苦味),其可能降低对设计用于降低口臭的症状的处理的顺应性。
对于所述没有胶基的完全水溶性区域特别有利的是由包衣组成,所述包衣包含以干重计70%以上的麦芽糖醇、优选以干重计85%以上的(总包衣的百分比)。在实施方案的一个备选的但同样有利的形式中,麦芽糖醇被吡喃葡糖基-甘露醇和吡喃葡糖基-山梨醇的混合物或木糖醇和甘露醇的混合物替代。
在10分钟的咀嚼中从如此配制的口香糖释放的MBE为(总MBE的)50%至80%。
有利的是,通过含超过80%的山梨醇、低于2%的阿拉伯胶和超过1%的锌盐(总微粒的百分比)的微粒,以口香糖的0.0005%至0.05%的量添加锌,所述微粒加至含胶基的区域。在10分钟的咀嚼中从如此配制的口香糖释放的锌为(总锌的)50%至80%。
其中至少15%的锌(总锌的百分比)作为选自氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌及其混合物的盐的离子引入微粒中,该微粒被直接引入含胶基的区域,且其余的量的锌被直接引入含胶基的区域的一种或多种氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌及其混合物携带的口香糖随时间推移也具有类似的释放。
因此,所阐述的实施方案允许可比量的MBE和Zn的同时释放,其能在口腔中产生协同作用。
含千日菊素或墙草碱的矫味剂的添加促进了活性剂的释放,并且特别被指出与薄荷矫味剂组合。
本发明还涉及治疗人口臭的症状的方法,其包括以下步骤:
1)将一个口香糖置于有口臭的患者的口腔中,所述口香糖至少由以下成分组成:
a)具有胶基第一区域,其具有由微粒提供的范围为口香糖的0.0005%至0.05%的锌含量,所述微粒含超过80%的山梨醇、少于2%的阿拉伯胶和超过1%的锌盐(总微粒的百分比);
b)不含胶基的第二区域,其由完全水溶性的包衣组成,特征在于其包含超过75%的麦芽糖醇、吡喃葡糖基-山梨醇和吡喃葡糖基-甘露醇混合物、或者木糖醇和甘露醇混合物,并且包含口香糖的0.02%至2%的木兰树皮提取物;
2)将所述的一个口香糖咀嚼10分钟,
所述口香糖在10分钟的咀嚼中能向口腔中释放其木兰树皮提取物含量的40%至80%(作为总提取物的百分比)和50%至80%(作为总锌的百分比),从而所述成分产生对抗口臭的症状的协同作用。
下文列出了含锌的微粒的实例、根据本发明的微粒、对比实施例和效用评价测试。
实施例1:本发明的口香糖中使用的微粒的组成
微粒的成分 | 实施例1 |
% | |
山梨醇 | 85.00 |
木糖醇 | 8.00 |
乙酰舒泛K | 1.00 |
矫味剂 | 0.80 |
绿色色素 | 0.20 |
阿拉伯胶 | 0.50 |
乳酸锌 | 3.10 |
水 | 1.40 |
总的微粒 | 100 |
以下表3阐述了本发明的口香糖组合物(实施例3)和参比组合物(实施例2)。所述口香糖采取填充的丸形式,其由三个分离的区域组成:填充物(没有胶基的区域)、核心(具有胶基的区域)和包衣(没有胶基的区域)。
百分比相对于单份的总量表示。以mg表示的值涉及重2.2g的一份,在所述实例中,其对应于一个。
治疗口臭症状的活性测试
使用OralChroma与参比口香糖(实施例2)对比测试本发明的口香糖(实施例3),以测量具有75ppb的最小口腔VSC值的志愿者的口腔VSC。测试市售产品,其由具有草本提取物(0.36%生咖啡豆和0.36%牛蒡(burdock))的无糖波状片剂组成。用于测定VSC的方法如上文所述。
结果在下表4中概述。
表4
在刚咀嚼后和1小时或2小时后,与(i)不含任何功能成分的口香糖和(ii)市售产品相比,本发明的口香糖能显著地将VSC的口腔浓度降低至更大的程度。
Claims (21)
1.口香糖,其由至少第一区域和至少第二区域组成,所述第一区域具有胶基,所述第二区域是没有胶基的、完全水溶性的,所述口香糖特征为存在a)和b)的协同组合:
a)有效量的选自木兰树皮提取物、绿茶提取物及其组合的植物提取物,
b)有效量的至少部分包含在完全水溶性的微粒中的锌离子。
2.根据权利要求1的口香糖,其中植物提取物是包含厚朴酚及和厚朴酚的木兰树皮提取物,优选地,以提取物的重量计厚朴酚及和厚朴酚的浓度高于80%。
3.根据权利要求1的口香糖,其中植物提取物是含儿茶素的绿茶提取物,优选地以提取物的重量计儿茶素浓度高于40%。
4.根据权利要求1-3中的一项或多项的口香糖,其中所述植物提取物包含在所述第二区域中。
5.根据权利要求1-3中的一项或多项的口香糖,其中所述植物提取物包含在所述第一区域中。
6.根据权利要求1-5中的一项或多项的口香糖,其中锌包含在所述第一区域中。
7.根据权利要求1-6中的一项或多项的口香糖,其中所述水溶性的微粒包含单独的或为其混合物形式的一种或多种多元醇、水胶体、矫味剂、染料、甜味剂和其他赋形剂,所述微粒具有低于1000μm的平均粒度分布。
8.根据以上权利要求中任意一项的口香糖,其中以重量计锌离子含量范围为0.0005%至0.05%,且植物提取物含量范围为0.02%至2%。
9.根据以上权利要求中任意一项的口香糖,其每单份包含0.012mg至1.2mg锌离子和0.5mg至50mg木兰树皮提取物。
10.根据以上权利要求中任意一项的口香糖,其中口腔气体中具有75ppb的最小VSC值的消费者咀嚼10分钟的单份能够在刚咀嚼后使口腔气体中挥发性硫化合物的平均浓度与咀嚼前的值相比降低至少40%。
11.根据以上权利要求中任意一项的口香糖,其中口腔气体中具有75ppb的最小VSC值的消费者咀嚼10分钟的单份在开始咀嚼后1小时能够使口腔气体中挥发性硫化合物的平均浓度与咀嚼前的值相比降低至少15%。
12.根据以上权利要求中任意一项的口香糖,其中锌离子以选自以下的盐存在:氯化锌、乙酸锌、乳酸锌、葡萄糖酸锌、丁酸锌、甘油酸锌、羟乙酸锌、甲酸锌、乳酸锌、吡啶甲酸锌、丙酸锌、水杨酸锌、酒石酸锌、硫酸锌、抗坏血酸锌、双甘氨酸锌、赖氨酸锌、苹果酸锌、单-L-甲硫氨酸硫酸锌、吡酮酸锌及其混合物。
13.根据权利要求8和9的口香糖,其中存在另外的锌盐,其选自:油酸锌、硬脂酸锌、柠檬酸锌、磷酸锌、碳酸锌、硼酸锌、草酸锌、天冬氨酸锌、氧化锌及其混合物。
14.根据权利要求13的口香糖,其中单份口香糖包含提供0.1至10mg的锌的量的所述另外的锌盐。
15.根据以上权利要求中任意一项的口香糖,其中所述具有胶基的第一区域形成核心,且所述没有胶基的完全水溶性的第二区域形成至少部分包裹第一区域的包衣层。
16.根据权利要求15的口香糖,其中超过70%重量的包衣层由麦芽糖醇、或吡喃葡糖基-甘露醇和吡喃葡糖基-山梨醇的混合物组成。
17.根据权利要求15或16的口香糖,其中填充物还存在于所述第一区域内部。
18.根据权利要求17的口香糖,其中所述填充物包含一种或多种的多元醇、赋形剂、乳化剂、维生素、包括锌盐的矿物盐、绿茶提取物和木兰树皮提取物、染料、酸化剂和矫味剂。
19.根据权利要求1-14中任意一项的口香糖,其中将所述第一区域和所述第二区域配制为重叠、交替的层的形式的区域。
20.根据以上权利要求中任意一项的口香糖,其包含至少一种选自以下的矫味剂:源自薄荷属、柑桔属、千日菊属以及薄荷醇的物种的那些、用作冷却和唾液分泌剂的人工和天然矫味剂及其组合。
21.根据权利要求1-20的口香糖,其用于治疗口臭症状。
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