GB2080681A - Oral compositions - Google Patents
Oral compositions Download PDFInfo
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- GB2080681A GB2080681A GB8024244A GB8024244A GB2080681A GB 2080681 A GB2080681 A GB 2080681A GB 8024244 A GB8024244 A GB 8024244A GB 8024244 A GB8024244 A GB 8024244A GB 2080681 A GB2080681 A GB 2080681A
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- Prior art keywords
- ascorbic acid
- mouthwash
- patients
- zinc
- oral
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K33/00—Medicinal preparations containing inorganic active ingredients
- A61K33/24—Heavy metals; Compounds thereof
- A61K33/30—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/27—Zinc; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/67—Vitamins
- A61K8/676—Ascorbic acid, i.e. vitamin C
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Inorganic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A therapeutic composition for topical oral administration having antibacterial and collagen production stimulating activity, comprises a pharmaceutically acceptable, water soluble zinc salt and ascorbic acid or an active analog thereof. The zinc salt and the ascorbic acid are present in an amount sufficient to provide a synergistic antimicrobial combination.
Description
SPECIFICATION
An oral composition for improving oral health
This invention relates to a composition for oral administration which improves the physiological tone of the oral tissues and which has an antimicrobial effect on the oral microflora.
All of the causative factors in the etiology of a health oral condition are not known. It is known, however, that a reduction in the amount of zinc ions or in the amount of ascorbic acid available to nourish the oral tissues adversely affects their physiological tone. How much of this is the result of enzymatic, microbial and other factors has not been determined. What has been clinically observed, however, is that sometimes the oral tissues become edematous, inflamed and susceptible to microbial attack.
It has been known for centuries that vitamin C deficiency causes scurvy. More recently, it has become known that the formation of normal collagen depends on ascorbic acid. Since ascorbic acid is involved in some hydroxylation reactions, the slowness with which scorbutics commonly heal may be caused by insufficient cross-linking in collagen due to decreased hydroxylation of proline.
It is known that a diet deficient in ascorbic acid or zinc renders the gingiva more susceptible to bacterial attack. Excess amounts of dietary ascorbic acid or zinc, however, do not increase the amount of these materials in the saliva and have no corresponding beneficial effect on the oral tissues.
There have been studies which have shown that the amount of zinc and vitamin C is depleted in the blood and in the cells by stress. It is also known that the plasma concentration of zinc decreases during pregnancy, and among some patients on oral contraceptives. Other studies have shown that zinc plays a role in the tast bud support system and in the mechanism of tastant-receptor binding. Zinc depletion is known to occur in patients taking drugs like
Dilantin or in subjects on diets heavy in fiber or phytate. Still other factors are known to interfere with the intestinal absorption or with the utilization of zinc ions as well as of ascorbic acid.
The physiological tone of the oral mucosa, however, is not the only factor in maintaining a healthy oral condition. Epidemiological studies have suggested that microbial plaque is a major factor contributing to dental caries and periodontal disease.
Numerous mechanisms by which dental caries may occur have been suggested. According to the most widely accepted concept, specific microbes present in bacterial plaque colonize the surface of the teeth, ferment dietary carbohydrates and produce organic acids. These acids demineralize the teeth, causing the enamel to decay.
Plaque is also implicated in periodontal disease.
Although the precise cause of periodontal disease remains unclear, it is widely accepted that the primary cause is bacterial plaque located in the gingival crevice between the surface of the teeth and the gingiva.
Mechanical debridement of plaque by brushing and use of floss is still the primary recommended and accepted method for the prevention of dental caries and periodontal disease. This approach is successful when rigorously practiced but is so highly labor-intensive that most people are not sufficiently motivated to practice it consistently. Since plaque is quickly reformed, continual brushing and flossing are essential to this method of therapy. Moreover, in the presence of gingival inflammation, mechanical methods of plaque removal frequently cause gingival hemorrhage. This often causes the patient to divert from his brushing and flossing regimen.
The focus in oral hygiene has been on a chemical method for dealing with oral plaque. While this clearly would have an obvious clinical advantage for use alone or more effectively in combination with mechanical methods, a more perfect therapeutic composition would also have a beneficial effecton the oral mucosa beyond that of a mere antimicrobial agent.
The problems in just dealing with plaque, however, should not be underestimated. In search of an effective chemical, it is important to keep in mind that the periodontal tissues may be colonized by as many as 150 different species of microorganisms.
The particular microbial flora in any given area of the mouth at any given time is the result of the micorbial succession that has taken place up to that time. Not all ofthe oral microflora are implicated in dental caries or in periodontal disease but those pathogenic genera which are responsible are, in general, among those most difficult to kill. Moreover, the net development of dental caries and periodontal disease is the result of the interplay of numerous organisms. From this, it is clear than an effective chemical method of just treating plaque must have a broad antimicrobial spectrum and be effective against those specific organisms that cause the problem.
In search of an effective chemical method for dealing with oral plaque, many chemicals have been tried. Several forms of antibiotics such as penicillin inhibit plaque formation, but the development of resistant organisms and patient sensitivity along with other side effects have seriously restricted their application.
To avoid the problems associated with systemic antibiotics, dental research has focused on antiseptics and on drugs uniquely involved in the biology of the mouth. Among the many materials tested for this purpose have been zinc salts and ascorbic acid. For example, zinc salts have been used as astringents in mouthwashes for the purpose of floccu lating and precipitating proteinaceous material so that it can be removed by flusing. Ascorbic acid has been tried in the prevention of dental plaque. U.S. patent No.
2,470,906 to R. Taylor.
Combinations of zinc salts with certain other antibacterial agents have been tried. U.S. patent No.
4,022,880 to L. Vinson et al. Still others have tried zinc salts with enzymes. U.S. patent No. 4,082,841 to
M. Pader. Oxidizing preparations containing ascorbic acid, a peroxide and a metal ion catalyst have also been tried. U.S. patent No. 3,065,139 to S.
Ericsson et al.
In view of the above, the object of the present invention is to provide a therapeutic composition for
use in improving the physiological tone of the oral tissues and for use in reducing oral plaque.
Accordingly, the present invention provides a therapeutic composition fortopical oral administration for stimulating production of collagen consist
ing essentially of about 0.5 to about 2.0 percent by weight/volume of a pharmaceutically acceptable, water soluble zinc salt and about 0.5 to about 2.0 percent by weight(volume of ascorbic acid or sodium ascorbate.
It has now been found that a combination of zinc ions and ascorbic acid provides a therapeutic composition which improves the physiological tone of the oral tissues as well as providing a therapeutic composition which is surprisingly effective against the oral microflora responsible for plaque. More particularly, it has been found that when these agents are combined a greater than additive antimicrobial effect can be obtained.
The provision of such a therapeutic omposition is a major accomplishment. For example, to be effective for the present purpose, the composition must provide an antiseptic with a broad antimicrobial spectrum. On the other hand, to avoid harming the mucosa, it cannot be too concentrated. Since, as such, it cannot be formulated strong enough to kill all of the organisms right away, it is important that it not be immediately cleared from the oral cavity but con tinues to be effective for some time thereafter. There is also the diluting effect of the saliva and the reinoculation of the oral cavity to contend with.
Since the composition may act by chemical combination with the mucosal and microbial protoplasm, it is important that the therapeutic composition not be inactivated by combination with the constituents of the saliva or exudates of the infections. Finally, it is important that the present combinations be shelf stable and compatible with pharmaceutical carriers and other ingredients normally found in oral prep arations. It is a further definite advantage that the combination is relatively inexpensive to formulate.
Insofar as known prior to the present discovery, it was not known that a combination of zinc ions and ascorbic acid could give rise to a synergistic combination if present at effective levels. Nor was it known that such a combination would provide a therapeutic effect after the combination is emptied from the mouth. While some of the benefits observed for higher levels of zinc and ascorbic acid may have been expected, there was no teaching in the prior art as to how those levels could be effectively raised in the oral cavity.
The therapeutic compositions of the present invention are non-toxic and innocuous tasting and they produce no normal irritation or allergic reactions. In the context of the present invention, ascorbic acid includes 1-ascorbic acid, dehydroascorbic acid and sodium ascorbate. Its active analogs include 1-glucoascorbic acid, daraboascorbic acid, 1-rhamnoascorbic acid, 6desoxy-1-ascorbic acid and the like.
Suitable zinc salts include those zinc compounds which are soluble in water at body temperature.
Suitable salts must be pharmaceutically acceptable.
As such, they must be safe and organoleptically tolerable in the oral cavity and have no stgniflcant side effects either orally or systemactically. Among the useful zinc salts are those formed from the following organic and inorganic anions: acetate, benzoate, borate, bromide, carbonate, citrate, chloride, glycerophosphate, hexafluorosilicate, phenol sulfate, silicate, alkanoates having Kto 18 carbon atoms, such as zinc stearate, sulfate, tannate, tita nate, tetrafluoroborate or the like. If the combination is to be stored, to prevent the oxidation oiascorbie acid, it is preferred that oxidizing zinc salts such as zinc perctide be avoided.It is also preferred that an antioxidact such as vitamin E be added. The zinc salts may be used singly or in combination but zinc sulfate usei alone is preferred.
In accordance w the present invention, the zinc salt and the ascorbic acid is present in that amount sufficient to provide a synergistic combnationteffec tive as an antimicrdiiiel agent against such diffIcult to kill oral microfloraiasActinomucesviscosus, alpha Streptococcus, Candida albicans, Escherichia coli, Pseudomonas aewginosa, Staphylococcus epidermidis and Streptococcus mutans.Excessive amounts of zinc salts beyond that necessary to provide an effective combination should be avoided since such compositions are unpleasantly astringent Similarly, excessive amounts of ascorbic acid should be avoided since such compositions are unpleasantly acid The pH of the mixture is preferably between about 4 and 5, most preferably about 4.5. This can be easily achieved by providing the ascorbic acid partly in the form of sodium ascorbate.
Normally, the zinc salt and ascorbic acid is in a pharmaceutical carrier which maybe either a liquid or solid. For example, wherethe oral composition is a mouthwash, the balance ef the preparation may consist of water, ethyl alcolid and a polyhydric alcohol such as glycerol or sorbitol. Flavoring agents and sweeteners may also be added along with stabilizers such as TWEEN 80.
The compositiomof tl e present invention can also
be formulated as apaste, powder or liquid dentrif
rice, chewing gum; tablet, lozenge orthe like. When the composition isaiathpaste, there may be pres
ent polishing aWsitbaming agents and so forth.
which are compatiI::lewiththe zinc salt and with the, ascorbic acid
In use, the tlbraEleutic composition is contacted
with the oral tissuesforseveral minutes and then
emptied. It has an irnmediate antimicrobral effect
and continuestoexert an antimicrobial and
therapeutic ^;tfor some time thereafter.
The following examples illustrate the invention.
Example 1 Amouthwashwas prepared from the following coumponents: 959L Ethyl Alcohol 200 ml ZnSOe7H,O 20 g
Ascorbic Acid 20 g
Glycerin 100 ml Waterq.s. 1000 ml
Example2
Twenty guinea pigs weighing 3 + 12 grams were treated with 4 ml of the mouthwash described in Example 1 twice daily for ninety days. The mouthwash was applied with a sterile cotton swab into the oral cavity of each animal.
The animals were sacrificed after ninety days. Tissues from the gingiva, salivary glands and mucosa of the oral cavity were obtained and fixed for histological examination. The results showed no pathological changes in the tissues and no irritation or edema as compared to ten control animals that received no treatment.
Example 3
To evaluate the mouthwash described in Example 1 for its effect in reducing oral plaque and in improving the physiological tone of the oral tissues, sixty patients were clinically observed. The symptoms and conditions presented by the patients were diverse but could be generally divided into five categories: ginigivitis periodontitis, periodontal abscess, acute necrotizing ulcerative gingivitis, juvenile periodontitis and desquamative gingivitis.
The patients were asked not to change any of their daily habits orto alter the intake of any medication that they were presently taking. Approximately half of the patients were given the mouthwash described in Example 1. These patients were instructed to use it twice daily, diluting it 1:1 with water, taking a mouthful, holding it in the mouth with agitation for two minutes and then emptying.
The other half of the patients were given a mouthwash like that described in Example 1 but without any ascorbic acid. These patients were also given liquid ascorbic acid and the instruction to put 4 or 5 drops of it in the mouth, hold it for two minutes and then swallow.
Most of the patients were observed at one-week intervals. Before treatment, typical symptoms of unhealthy gingiva were swelling, mild to gross edema and mild to frank hemorrhage. A majority had an obvious disagreeable mouth odor and all had a desire to improve. Consequently, it can be assumed that they were reasonably consistent in the use of the mouthwash and the ascorbic acid as directed.
Those patients with extreme pathological conditions showed marked improvement in 1 to 3 days. In all cases, there was a marked clinical improvement at the end of one week. In most instances, the frank hemorrhage had stopped, edema lessened, appearance of stippling increased and color begun to change from bright red to a lighter pink. At the end of the second and third weeks, the improvement was even more evident.
Without exception, each of the patients said that his mouth and teeth felt cleaner, fresher and more comfortable even after the first day but markedly so after several day's use. All wanted to continue to use the mouthwash. The gingival and periodontal index was determined by the technique described by J.
Silliness et al, Acta. Odont. Scant.22, 121 and by photography before each patient used the mouthwash and 2 weeks, 1 month and 3 months after using the mouthwash. With disclosing wafers, there was obvious clinical evidence of less bacteriological plaque accumulation after using the mouthwash. Plaque accumulation decreased consistently as the patient continued to use the mouthwash.
Example 4
To evaluate the mouthwash described in Example 1 for its effect in killing oral bacteria, twenty-three patients ranging in age from 19 to 52 years were tested. The patients were divided into two groups.
The patients in Group I were given a placebo mouthwash like that in Example 1 but with no zinc sulfate or ascorbic acid. Those in Group II were given the mouthwash described in Example 1.
Each patient was asked to rinse his mouth with the mouthwash for 2 minutes and then to empty. A swab culture was taken before and at 5, 10 and 30 minute intervals after using the mouthwash. The results are reported in Table I below and show that the mouthwash described in Example 1 significantly decreased the bacteria in the oral cavity even after the mouthwash had been discharged.
Table I
Number of Bacterial
cells/ml
Group I Group lI Before using mouthwash 4.8 x 107 t 0.98 4.9 x 107 + 0.78 5 minutes after mouthwash 4.7 x 107 + 0.65 3.1 x 106 + 0.45 10 minutes after mouthwash 4.9 x 10' + 0.74 1.3 x 108 0:61 30 minutes after mouthwash 4.8 x 107 i 0.34 0.5 > < x 106 106 t 0.04 Example 5
Seventeen pregnant women, ranging in age from 20 to 32 years, in the third trimester, suffering from pergnancy gingivitis were examined and classified into one of two categories. Those with gingivitis without any hyperplastic signs and those with gingivitis gravidarum.Seven of the patients were classified as having gingivitis without any hyperplastic signs and ten patients were classified as having gingivitis gravidarum with hyperplastic signs.
Patients were divided into two groups for treatment. Three patients from the first category and five patients from the second category were given daily amounts of 50 mg of ZnSO4.7H2O and 100 mg of vitamin C orally for one month.
The remaining nine patients were given the mouthwash described in Example 1 and instructed to use it twice daily.
The treatment with orally administered zinc sulfate and ascorbic acid was not effective. There was no increase in the zinc or ascorbic acid levels in the saliva but there was an increase in the blood level due to the treatment.
With the other patients, bleeding stopped after one week and the gingiva returned to its normal pink coior after one month. Ascorbic acid in the saliva increased from 15.6 Ccg/gram to 31.2 CLglgram and the zinc level in the saliva increased from 10 yg/gram to 18.6 ,ug/gram. Hence, it is seen that treatment with the mouthwash of Example 1 during pregnancy has a greater effect than treatment with zinc salt and vitamin C orally.
Example 6
Eleven patients suffering with canker sores, not of herpes simplex origin, were instructed to rinse three times a day with the mouthwash described in Example 1. After one day, the patients were relieved and could drink acidic liquids such as orange juice which had been painful before. After four days, the canker sores were completely healed and the treatment was stopped.
In the first year, the patients had recurrent canker sores sixtimes. Each time, the sores were treated for four days. In the second year, they experienced recurrence two times, in the third year there was no recurrence. The patients have been followed four years. To date there has been no recurrence.
Eight other patients with canker sores, not of herpes simplex origin, were instructed to use the mouthwash described in Example 1 twice a day, once in the morning and once before bedtime. In the first year, the patients experienced recurrent sores three to four times a year. In the second year, there has been no recurrence.
Example 7
Sixteen men suffering with throat infection were given the mouthwash described in Example 1 and advised to use it twice a day for a week. Before treatment, swab cultures revealed heavy growth of alpha Streptococcus, Staphyllococcus epidermidis,
Escherichia coli and Candida albicans.
At the beginning of the treatment, some of the patients could not swallow food due to the infection.
Twenty-four hours after using the mouthwash, the situation has eased. All patients could eat normally after two days. After six days, swab cultures revealed no growth ofthe abovernantioned organisms. No adverse side effects or discomfort because of the treatment was noted.
Example 8
A mouthwash was prepared from the following components:
95% Ethyl alcohol 200 ml ZnSO4.7H2O 20 g
Ascorbic acid 20 g
TWEEN 80* 100 ml
Vitamin E 1,000 l.U.
water, q.s. 1;,0Q0 ml potyoxyethylane sorbilan monooleate
Example 9 Sixty-three patients ranging in age from 40 to 68 years were tested for taste acuity determined by measurement of the detection and recognition thresholds for four taste qualities: NaCI for salt, sucrose for sweet, HCI for sour and urea for bitter.
Twenty-two of the patients had normal taste and 41 had idiopathic hypogeusia.
Each of the hypogeusia patients was instructed to rinse his mouth twice a day with the mouthwash provided therefor. To note the placebo effect, nine of the idiopathic hypogeusia patients were given a placebo like the mouthwash described in Example 8 but without zinc sulfate or ascorbic acid All of the other patients used the mouthwash described in
Example 8. Parotid saliva was collected before treatment and one and three months after treatment.
The results are reported in Table II below. The hypogeusia patients receiving the placebo did not improve during the3 month trial period butthe taste of the patients using the mouthwash described in
Example 8 improved after one month and became normal afterthree months Table Zinc Concentration ppb in Saliva
Three
Mouthwash Before One Month Months
Normal Placebo 49 + 16 53 + t2 50 + 18 Hypogeusia Example 18 13 38i10 10 47i13 Example 10
In this example, zinc sulfate and ascorbic acid was checked for its effectiveness on two of the bacterial species known to be implicated in dental plaque.
These results were then compared with the effect of a synergistic combination of zinc sulfate and ascorbic acid.
Culture media were prepared with ZnSO47H2O or ascorbic acid or a combination thereof in Tryplic Soy
Broth and in a concentration of 0.5, 1,2,4,8 or 10 percent by weight/volume. These broths were then placed in 1 ml tubes and 0.001 ml of an inoculum containing 1 x 10' alpha Streptococci cellslml or the same concentration of Staphylococcus epidermis was added to the tubes. The tubes were then incubated overnight and the bacterial growth was determined the next day.
All of the tubes showed no growth in the strepto cocci-inoculated media in the presence of all levels of zinc sulfate or ascorbic acid. In the case of the staphylococci-inoculated media, 80 percent of the cultured bacteria were killed in the presenceof0.5 percent by weightlvolume of ZnSO47H2O or ascorbic acid.
When the concentration of the ZnSO47H2O or ascorbic acid was increased to 5 percent by weightlvolume, all of the staphylocwci were also kil- led. The same result, however, was obtained with a combination of 0.5 percentZnSO+7Owith 0.5 0.5 percent ascorbic acid. This indicates a synergistic effect between zinc ions and ascorbic acid in their antimicrobial activity against the organisms tested.
Example 1J In this example the effect of the mouth wash pre- pared in Example 1 was tested against the same bacteria as in Example 10. An 0.001 ml aliquant of a staphylococcus inoculum containing 6 x 10" cells/ml or a similar aliquant of a streptococcus inoculum containing 4.2 x 10'0 cells/ml was added to a test tube.
A volume of the mouthwash described in Example 1 was added to each tube such that the concentration of ZnSO4.7H2O and ascorbic acid were both 0.5 percent by weight/volume. In another set of experiments, the mouthwash of Example 1 was diluted with water 1:1 such that the concentration of the zinc sulfate and acid was half of that described above.
The concentration of the bacteria was then deter mined after 30 sec and after 1, Sand 30 minutes.
The results are reported in Table Ill below.
Table 111 30 sec imin 2 min Smin 30min Mouthwash from
Example 1
Concentrated
Staphylococcus NG* NG NG NG NG
Streptococcus 3 x 106 NG NG NG NG
Diluted 1:1
Staphylococcus 3x106 4x106 9x104 6x104 1x103 Streptococcus 1.5 x 106 2.9 x 106 2.3 x 106 NG NG
No Growth
Example 12
Culture media were prepared with ZnSO4.7H2O or ascorbic acid or a combination thereof in Tryplic Soy
Broth as described in Example 10.These broths were then inoculated with 0.1 ml of an inoculum containing 8 x 106 cells/ml of Escherichia coli ATCC-25922 or 5 x 108 cells/ml of Pseudomonas aeruginosa. The results are reported in Table IV below wherein and throughout the following examples the symbol H + indicates that there was heavy growth, M + moderate growth, S + scant growth and NG that there was no growth.
Table IV
Concentration percent by weightlvolume Q25 0.5 1.0 2.0 4.0 8.0 Control ZnSO4.7H2O E. Coli H+ NG NG NG NG H+
P. aeruginosa - H+ S+ S+ S+ S+ H+
Ascorbic acid
E.Coli S+ H+ NG NG NG H+
P. aeruginosa - H+ M+ S+ NG NG H+
Combination
ZnSO4.7H2O and ascorbic acid E.coli H+ M+ S+ NG NG - H+
P. aeruginosa S+ S+ NG NG NG
Example 13
The effectiveness of the mouthwash described in
Example 1 was tested for its antimicrobial effect on
Streptococcus mutans, ATTC No. 25175, Actinomyces viscosus, ATCC No. 19246 and Candida albicans, ATCC No. 18804. It was found effective in inhibiting the growth of all of the test organisms.
Example 14
The effectiveness of zinc salts, ascorbic acid and a combination thereof was tried in an amount below that necessary for a synergistic combination. More particularly, ZnSO4.7H2O, ascorbic acid and combinations thereof were tested atthe 0.1, 0.2, 0.3 and 0.4 percent by weight/volume level for its antimicrobial effect against alpha Streptococcus, Streptococcus muta ns, Staphylococcus aureus, Sta phyloocccus epidermidis, Actinomyces israelis and Actinomyces viscosus. All samples showed heavy growth with zinc alone, ascorbic acid alone or their 1:1 combination at the 0.1, 0.2, 0.3 and 0.4 concentrations.
Example 15
The effectiveness of the mouthwash described in
Example 1 in the presence of biological fluids such as sterile animal serum was tested for its antimicrobial effect on alpha Streptococci and Staphylococcus epiderm idis. It was found that the mouthwash was effective against these organisms in the presence of the serum.
Example 16
Ascorbic acid when dissolved in water tends to oxidize and is not stable for a long period of time.
However, when ZnSO4.7H2O is added to an ascorbic acid solution, it becomes more stable. Stability can be extended to one year by adding 1000 1. U. Vitamin
E per liter of solution containing 0.5 percent by weight/volume of ZnSO4.7H2O and of ascorbic acid.
The results of these tests are reported in Table V below.
Table V
Active Ascorbic Acid
0 1 month 3months 6months 1 year 2% Ascorbic
acid 20 16.6 15.4 12.2 10.1
2% Ascorbic
acid and ZnSO4.7H2O 20 20 19.8 18.7 17.6
Moutwash
Example 1 20 20 20 19.6 18.4
Mouthwash
Example 18 20 20 20 20 19.5
From the above, it is seen that TWEEN also increases the stability of the vitamin C.
In view of the above, it will be seen that the several objects of the invention are achieved and other advantageous results attained. As various changes could be made in the above compositions and methods without departing from the scope of the invention, it is intended that all matter contained in the above description shall be interpreted as illustrative and not in a limiting sense. The invention accordingly comprises the compositions and methods hereinbefore described, the scope of the invention being indicated by the subjoined claims.
Claims (5)
1. Atherapeutic composition for topical oral administration for stimulating production of collagen consisting essentially of about 0.5 to about 2.0 percent by weightlvolume of a pharmaceutically acceptable, water soluble zinc salt and about 0.5 to about 2.0 percent by weightlvolume of ascorbic acid or sodium ascorbate.
2. The composition according to claim 1 wherein the ratio of the zinc salt to the ascorbic acid or sodium ascorbate is substantially 1 to 1 by weight
3. The composition according to claim 2 wherein the zinc salt is ZnSO4.7H2O.
4. The composition according to claim 3 wherein the pH is from about 4 to about 5.
5. Atherapeutic composition for topical oral administration according to claims 1 and 2 substantially as herein described with reference to the examples.
Priority Applications (1)
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GB8024244A GB2080681B (en) | 1980-07-24 | 1980-07-24 | Oral compositions |
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GB8024244A GB2080681B (en) | 1980-07-24 | 1980-07-24 | Oral compositions |
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GB2080681A true GB2080681A (en) | 1982-02-10 |
GB2080681B GB2080681B (en) | 1985-07-10 |
Family
ID=10515006
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Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4997640A (en) * | 1987-12-18 | 1991-03-05 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Oral compositions |
EP0425002A1 (en) * | 1989-10-06 | 1991-05-02 | Unilever N.V. | Oral compositions |
WO2000074639A1 (en) * | 1999-06-07 | 2000-12-14 | University Of Southern California | Composition and method for treating dental caries using inorganic metal salts |
WO2001089520A2 (en) * | 2000-05-19 | 2001-11-29 | Progenics Pharmaceuticals, Inc. | Dehydroascorbic acid formulations and uses thereof |
US8168161B2 (en) * | 2004-12-22 | 2012-05-01 | Hill's Pet Nutrition, Inc. | Method to promote oral health in companion animals |
RU2650998C2 (en) * | 2016-03-30 | 2018-04-18 | Общество С Ограниченной Ответственностью "Анвилаб" | Pharmaceutical composition for local application with antibacterial, anti-inflammatory and immunomodulating action |
US10406200B2 (en) | 2012-10-29 | 2019-09-10 | The University Of North Carolina At Chapel Hill | Methods and compositions for treating mucusal tissue disorders |
-
1980
- 1980-07-24 GB GB8024244A patent/GB2080681B/en not_active Expired
Cited By (11)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4997640A (en) * | 1987-12-18 | 1991-03-05 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Oral compositions |
EP0425002A1 (en) * | 1989-10-06 | 1991-05-02 | Unilever N.V. | Oral compositions |
US5094842A (en) * | 1989-10-06 | 1992-03-10 | Chesebrough-Pond's Usa Co., Division Of Conopco, Inc. | Oral compositions |
WO2000074639A1 (en) * | 1999-06-07 | 2000-12-14 | University Of Southern California | Composition and method for treating dental caries using inorganic metal salts |
WO2001089520A2 (en) * | 2000-05-19 | 2001-11-29 | Progenics Pharmaceuticals, Inc. | Dehydroascorbic acid formulations and uses thereof |
WO2001089520A3 (en) * | 2000-05-19 | 2002-09-12 | Progenics Pharm Inc | Dehydroascorbic acid formulations and uses thereof |
US8168161B2 (en) * | 2004-12-22 | 2012-05-01 | Hill's Pet Nutrition, Inc. | Method to promote oral health in companion animals |
US10406200B2 (en) | 2012-10-29 | 2019-09-10 | The University Of North Carolina At Chapel Hill | Methods and compositions for treating mucusal tissue disorders |
US11058743B2 (en) | 2012-10-29 | 2021-07-13 | The University Of North Carolina At Chapel Hill | Methods and compositions for treating mucosal tissue disorders |
US11938166B2 (en) | 2012-10-29 | 2024-03-26 | The University Of North Carolina At Chapel Hill | Methods and compositions for treating mucosal tissue disorders |
RU2650998C2 (en) * | 2016-03-30 | 2018-04-18 | Общество С Ограниченной Ответственностью "Анвилаб" | Pharmaceutical composition for local application with antibacterial, anti-inflammatory and immunomodulating action |
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GB2080681B (en) | 1985-07-10 |
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