DE3310182A1 - Pharmaceutical composition for treating dental caries - Google Patents

Abstract

The present invention relates to the area of stomatology. The pharmaceutical composition according to the invention for treating dental caries is composed of an active substance, of a mixture of sodium monofluorophosphate and of an anticaries agent which is a product which is prepared by treating the bone tissue with a dilute mineral acid until there has been complete dissolution of the mineral components and water-soluble proteins which are present in the bone tissue, by separating the prepared solution and diluting it with water with the addition of citric acid or its salts as stabiliser and subsequently neutralising the solution and drying. The said composition is used for the prophylaxis and treatment of dental caries by oral intake.

Description

MEDICINAL PRODUCTS FOR TREATMENT OF CARIES OF TEETH

The invention relates to the field

of otoiaatologie, and in particular relates to a medicinal product for .treatment of caries of the teeth, that .for propnylaxis and treatment of tooth decay by the ptroral Oral use.

Are known agents for the treatment and verscniedene Pro pnylaxe for peroral oral use in tablet form, comprising as an active ingredient sodium fluoride. / Farmacopea romana, 1972, p.460, British pharmacopeia, 1973, Ρ · 4Jl /.

Also known is a drug for the treatment of tooth decay in tablet form "Calcipot-F" / Leipzig, Germed, GDR /, which contains calcium and fluorine compounds as active ingredients. The medicinal product has the following composition in grams:

Calcium hydrofaen phosphate - 0.29

calcium nitrate - 0.05

calcium lactate - 0.01

Sucrose - 0.50

- lactose - 0.04?

Magnesium silicofluoride - 0.0024

Total weight of one tablet is 1 gram.

The said means is characterized by a low Anti-caries effect, thanks to a low concentrate ion of fluorine, calcium and phosphorus ions in the oral cavity fluid, by an insignificant increase in the resistance of the firm and soft tissues and by a low reduction in the cariesogenic activity of the dental plaque. The main object of the present invention is the development of a drug that has a high anti-caries effect which makes it possible to increase the resistance of the firm and soft tissues of the oral cavity.

Another object of the present invention is to develop a medicament which enables to reduce the cariesogenic activity of the plaque.

The invention is based on the object of a means for treating the by the choice of a new active ingredient To develop caries of the teeth, which has a high level of anticaries- ^ v

.- * OO IU ΙΟΛ

Help Vbv β * ■ * * * *

has effectively, which makes it possible to increase the resistance of the solid UNU soft tissues of the r.iundhöhle and α ie kariesogene activity of Zahnbelä _b to reduce 'e.

This object is achieved by uaß the medicament for the treatment of tooth decay, which contains an active ingredient and a pharmaceutical diluent, according to the invention the active ingredient is a mixture of liatric monofluorophosphate and anti-caries, which is a product represents that by machining any bone tissue rdiluted mineral acid until the mineral components and the water-soluble proteins are completely dissolved, contained in bone tissue, by separating the prepared solution, diluting it with water with the addition of a stabilizing agent, citric acid or their salts, and subsequent neutralization and drying the solution is prepared and the following components in wt.%: Calcium 2-6

Sodium 19-23

Potassium 0.04-0.13

Anion of mineral acid (chlorides) 6-10.6 Anion of orthophosphoric acid 1.5-5.0

water-soluble proteins 1.0-5.0

Magne s1um 0.05-0.2

Complex of trace elements,

including fluorine, manganese, tin, zinc and iron 0.01-0.02

complex citrate compounds, i

Converted to an anion of citric acid everything else

with a ratio of the active ingredient to the pharmaceutical Diluent 1: 23.5 - 1: 24.5.

When using the drug in the form of tablets, it should preferably contain the active ingredient in grams each Tablet contain:

Sodium Aonofluorophosphate - 0.0065-0.0075

Anticarious agent - 0.16-0.10.

Desirably should be considered pharmaceutical

BATH

Filling compound starch and lactose can be used.

The drug is intended to be in the form of tablets related dragees are taken orally.

The tablets of the invention are white

^ Color with no smell a little sweet taste, £ \ xt soluble in water and Speicnel. When using the tablets, it is desirable to chew them. When chewing for 2-2 minutes, the local treatment effect occurs, and after ingestion, the general effect, which increases the resistance of the firm and soft tissues of the oral cavity and reduces the cariesogenic activity of the plaque.

The agent according to the invention for the treatment of caries the teeth allows the concentration of the pluorion ions 6-7 times, calcium ions 2 ~ 2.5 times, phosphorus ions twice as much as the known preparation "CaI-cipot-JF" to increase the anti-caries effect compared to the known preparation to increase by 2 times, the permeability of the tooth enamel compared to the known preparation by 3 times to reduce and the cariesogenic activity of the plaque compared to the known preparation

to decrease 2 times. The agent according to the invention and the anti-caries in its composition were used on animals and tested experimentally on people in clinics.

A 5% solution of the anti-caries substance was tested, that in the composition of the agent according to the invention is present compared to the control. The test was carried out on 80 one-month-old »Vi st ar -Eat (40 rats with the invention Solution and 40 rats with control solution)

PQ led. All animals received a cariesogenic putter ration Stephan-580 and the solutions according to the invention were applied to the teeth of the rats for 4% per day for 3 minutes. After the end of the experiment, the teeth were removed and the caries index was determined using a generally applicable method. The results obtained in this experiment are shown in Table 1.

l'abelle 1

Comparative data on anti-caries effectiveness the solution of the invention Ant ikariessGoffes towards the Control solution

YY I U I ÖZ

Serial Name of the Know digits No. Preparation In the. Area of Fissures /Groups/ Caries index Anticaries effec-
tivity, io I. 2 3 4th 2 Control group 26.75 - 3 Solution of the anti
caries,
according to the invention 20.42 23.7

Code number Table 1 In all
total (Cont O Serial In the field of
Contact zones e r η Kr .. Zones into the-

Caries anti-drug index Rieseffektiv.itat, %

Caries-Antikarie sindex effectiveness,

2.76 1.00

63.7

21.42

27.4

Caries prophylactic effectiveness of erfindungsgeiüäßen anti-caries substance in the form of a ^ fhigen solution for applications is in the application during 1.5 years twice a month in children aged 7-10 years according to the indicators of the relative reduction 'of the increase of DiViF T-indices of s 44.1 to 53.7% and according to the DiVIF-S ₇ index from 40.2 to 58.0%, with the acid resistance of the teeth increasing significantly according to the GRT test.

BATH ORIGINAL

The effectiveness of the solution of the anti-caries substances is high when treating the earlier stages of the anti-caries; the positive treatment effect, best in the disappearance or in the reduction of demineralization spots, was in 1 / 2,4-4 #, the stabilization of the process in 14-31,9 # and the lack of the treatment effect in 2% of the cases.

Effectiveness of fig solution of anti-caries substance in the treatment of hyperestesis of solid tooth tissues is good; increased sensitivity of the tooth necks will result Completely eliminated 25.2-36.4% of cases.

Clinically, the anti-caries substance was used to study his prophylactic effect in children and pregnant women as well as to study its effectiveness in treatment of foci-shaped demineralisation foci of the tooth enamel tried. The anti-caries substance was in the form of 1.5-3% strength Solution used for applications.

In accordance with the results of the epidemiological Investigations were 176 children aged 7-8 years-2? chosen. The children were divided into two groups: The first group included children with whom one had the Has applied the anti-caries substance - 81 Children;

The second group of children was a control group of 95 children.

The applications with the solution were carried out after brushing the teeth with a hygienic toothpaste. The teeth were isolated from the saliva with lignin balls and dried with an air jet. With the help of spoons made of elastic plastic, in which heavily wetted loose cotton balls are housed, the solution was applied to all surfaces of the teeth. The duration of the applications was 10 minutes for each Jaw. After the applications, the children were advised to Do not eat or drink for 2 hours after treatment. After this r.iethodik, all subsequent applications Performed once in two weeks.

When the oral cavity was examined for the first time, a re _

■ · W ■ * «<« * V (I "■ · Mw * ·"

- fa -

Relatively the same gray of the damage to the cezirins by caries from 1.12 + 0.13 to Ι, ^ Ο + Ο, Ι * according to DIiP-T.

The results of the application of the anti-caries solution are reflected in Table 2.

The table shows that the reduction in Increase in caries in the first group of children 44.7 / ϊ and 49.5% according to DMF-T and DaDf-fci.

In the analysis of the anticarial effect of the subject to be examined The substance in relation to the individual groups of teeth was its effect on both the beginning of the Examination of already erupted first molars as well as the incisors that erupted during the observation are established.

The solution of the substance according to the invention was for the I ^ Treatment of the detainer al isation of teeth in 81 pupils used between the ages of 7-14 years.

The children were divided into two subgroups divided by the form of the itemineralization:

In group-j5a there were children with a slow-moving one Demineralization / 42 students in total /;

• Table 2

Intensity of tooth decay of the fences during the disease

Serial Grief Cnarak code numbers according to 1 growth
Caries year of observations Kr.: The
group ^{ter the} number
through- ·. _T ,
the un- ..YYHM D the Reduction of the
Growth,% leading _examination _
prophylactic. , ms DMF-T DIvIF-S tables measures 5 1 2 6th 7 a 2 I. Application nen the tough no with one reminerali- sender Solution of the invention o, i6 appropriate substance oil
fes 0.97 +
0.14 1.22+
0.2a 19.6 22.7 3> II Control 95 0.24 - -

2 courts.)

Lfd indicators after 3 years of observation

Number of un- Increment of 'Reduction of

examined tooth decay increment, 70

DiVIP-T D * 1F-Ü DiIF-T Ditf

10 11 12 13

81 1.61+ 2.59+ 44.7 49.5

O ₁ Io 0.34

? a 2.91+ 5.13+

0.16 0.25

In group 3b there were children with rapid progression Demineralization (39 students in total).

A total of 229 teeth were demineralized

of the children of the JJa group and on 248 \ teeth of the children

of the 3b-G group / Table 3 /. To the control group belonged to children, as in the previous study, labeled la and Ib groups in the table are.

To achieve a positive result of the treatment the teeth with the solution of the substance according to the invention was on average the execution of IO-I5 applications in the 3a group and 20-25 applications in the 3b group. ___

- ii -

Table 3

Number of teeth of the children of the 3 · group and the 1st control group with local deminerslisat ions depending on their size

Serial
Ii r ... Size of
stains number of teeth
lisat 48
102
155 with local
ions Deiüinera- la control lb control
group group 305 3a group 3b group 2
3
4th <2 mm ²
2-3iam ²
> 3 mm ^ 73
125
81 81
117
31 24
120
104 5 stains
all in all 279 229 248

Remineralizing therapy was effective in treating the slow process of demineralization. Whereby the spots of small dimensions ( < 2mm

ρ
and 2-3 mm) disappeared and decreased faster than large-sized spots. Conservative treatment of the rapid demineralization of the teeth of the children in the 3b group was less effective, but the direct correlation between the effectiveness of the treatment and the size of the stains was also maintained in this group (Table 4).

The positive effect of the treatment, the disappearance of the stains in the 3a group, was observed on 193 teeth \ of. 229 (84 ^ + 2.4) compared to the control group, in which the positive result of the treatment was found on 100 teeth out of 270 (36% + 2.9).

The stabilization of the process in the 3a group took place on 31 teeth (14 ^ 6.23) and on 87 teeth (31% + 2.8) in the control group.

The enlargement of the spots and the formation of cavities occurred in group 3a only on 5 teeth of

229 (2% + 0.9) and in the control group 92 of

279 Zannen (33 ^ + 2.8).

The difference is evident in the indicators of the> a group and the Konirollgruppe Ia is statistically identifiable (Table 4).

In the 3b group, the rapid demineralization gave a positive result in 155 teeth out of 24a (637 ± -3 ''), while in the control group a spontaneous blurring of the spots was observed in 33 of 205 teeth, which was only 11/0 + 1.8

mattered. In 60 teeth from children of the j) b group (24/0 + 2.7) XO -the process has stabilized. Cavities were formed in the area of local demineral ions of 33 teeth (13% + 2.1) of the children of the 3D-G ^- I ¹ UPPe.

The differences between the indicators of the 3b group ^ pe and the control group Ib are statistically detectable.

This is the positive average result in the treatment of the rapidly running denineralization of tooth enamel 73 »5% ·

Studies have been carried out the solution of the anti-caries substance in pregnant women. After an epidemiological investigation of the pregnant women it was found that with increasing. During pregnancy, the frequency and intensity of local enamel demineralization increases. For the prophylaxis of this damage, the solution of the substance according to the invention was used in the form of applications in 69 women (group I), a group of 64 pregnant women served as control group II.

By examining the women of the two groups (pregnancy 1-3 months) a relatively equal one was found Degree of damage to teeth with local ^ demineralizations of enamel 29-30 / &, with average Damage to 1.8-0.3 teeth detected.

At the end of pregnancy, the local demineralizations wax of the enamel in women of the control group in 64% of the cases with an average index of 5.23 + 0.7 teeth were recorded.

The application of the η anti-caries substance according to the invention in women in group I it not only enabled the development of new local damage to the tooth enamel

Serial
Kr.

-13 -

Table 4

The results of the treatment of the children's teeth in accordance with remineralised solutions _and the anti-caries effect according to the invention

Characteristic of the local de-mineralization ions

Result of the

treatment

the deiuine distribution of the spots

ralization children of the 3a group

of the tooth _{scraper- according to size}

zes - ~ 2 ^ -> -z 2 ν-, 2

According to the number t in the

2mm

Abs. M + m, % equal to the control / p <0.001

disappear 64 98 the stain stabilization 13th ia of the process 4th 1 formation of Defects

193 04 + 2.4 10.8

31 14 + 2.3 4.5 5 2 + 0.9 fa, 9

Overall:

229 100

-Ή 1 "

i. υ hurry 4

Serial Characteristics of the local JJ mineralizations

Distribution of blecke in children of the 3b group

Big awake

² now 2 2-3mm

By number

Paragraph M + m,

t compared to control / p <0.001 /

10

19th

12.8

24 + 2.7

3.4

16

13 + 2.1

.14.7

100

BATH ORIGINAL

^ en, but also to stabilize the process in the existing spots / there was no enlargement of the local de; :: ineralizations and emergenceUn ₁ J vun Kavitäi. en observed /.

Investigations into the influence of the invention were also carried out Anti-caries in tablet farm on the main functions of the organism of animals in acute and chronic trials. The acute experiments were carried out on two species of animals, on white mice and on Rats, and the chronic experiments carried out on three species of animals, rats, guinea pigs and young dogs. A total of 4 species of animals were examined subjected. Different methods, toxicological, biochemical and histological, were used Investigations have been carried out that the harmlessness of the preparation.

Acute toxicity of the anti-caries substance according to the invention in the form of a 30% aqueous suspension became white Mice, female and male, with a mass (weight) of 15-31 g when introduced orally with the aid a metal probe, calculated for doses of 6000 mg / kg, 8000 mg / kg, 13000 mg / kg, 14000 mg / kg, 15000 mg / kg and 16000 mg / kg were examined. The use of larger doses was not possible because the maximum amount of the suspension to be introduced was exceeded. The observations of the animals after the introduction of the suspension was carried out for 10 days. All this time the animals received \ the usual food and drink for them.

The index of acute toxicity (LDc _n ) can be

Do not calculate pO because even with the introduction of the preparations in the highest doses there was no fatal outcome. Only when the suspension of the anti-caries tablets, calculated at 16,000 mg / kg, was it possible for two of the six mice to

^ 5 occur from tremor and the temporary paralysis of the hind paws watch. The other doses did not cause any changes in the behavior of the animals.

The results of the experiment show that the

-Ib-

Ant ikariesmit tel according to the invention in tablets for peroxal . Introducing a little toxic preparation.

The acute toxicity of the anticaries agent according to the invention was investigated on hats, female and male, weighing 90-110 g. The preparation was made up in the form of a ^ 0% aqueous suspension. The following preparation doses were introduced: 14500 mg / kg and 16000 mg / kg. The animals were observed for 10 days. During the observations, the animals received the usual feed ration. No fatal outcome was recorded during the 10 days of observation. In the first 2-2 hours the animals were not very agile and tired. The ItDc ₀ index could not be calculated because the maximum permissible drug doses did not cause any fatal outcome. The anti-caries agent according to the invention is not very toxic when introduced by psoroid.

The study of the chronic toxicity of the agent according to the invention was carried out on 3 species of animals: on young guinea pigs, rats and young dogs. The results of the investigations showed no changes in weight gain and no changes in the general condition of the animals. The hämatölogisehen investigations (number of erythrocytes, leukocytes, hemoglobin, erythrocyte sedimentation rate. And Le ukozytenfärmel) and the biochemical blood count and urinalysis of animals have shown no pathological changes. A prolonged oral introduction of the anticaries agent according to the invention did not affect the circulatory and endocrine systems or the blood-forming organs. In the organs of animals killed no significant T) Q pathological changes were detected. The anti-caries agent according to the invention has no irritant or allergy properties.

The means according to the invention was compared to humans tested for the effect of the well-known preparation "Calcipot-F".

To investigate the dynamics of the transition of the active ingredients of the tablets into the oral cavity fluid Tests of oral fluid in 20 students

ijtomatologen & -leicii after chewing the tablets of the known Composition and the agent according to the invention guided. Thereby one determined the weight of ionized and hydrolyzable fluorine in an electrochemical process with fluorine-selective electrodes: content of phosphorus with an epektrophotometric and content of Ca with a Atomic absorption process.

The investigation of the effect of the preparations to be examined on the permeability of the tooth enamel at 45 approx was performed on 24 teeth (canines) of 6 dogs aged 2-4 years after a single 30-minute treatment carried out with an aqueous pulpy mass from the agent to be examined. Then the percentage the permeability calculated in comparison to the control (on the teeth to which no agent was applied).

The anti-caries effectiveness of the preparations to be compared and the intensity of the transition of the fluorine compounds into the superficial layers of tooth enamel (as well as the Acid resistance of tooth enamel) were found in 75 Wistar rats examined the cariesogenic feed ration Stephan-580 for 4 weeks beginning at the age of one month (25 rats each in test and control groups). In test animals, a suspension of tablets of known composition or that of the invention was used Applied daily with a brush to the teeth for 1-1.5 minutes. After completing the experiment, the teeth were removed and the caries index was determined according to "a general methodology, in the electrochemical process also became the content of fluorine in the surface layer of the tooth enamel determined after the biopsy.

The acid resistance of the tooth enamel (CRT test) was assessed according to the Mühlemann and Wolgensinger method (Mühlemann, Wolgensinger, HeIv. odont., Acta, 1959 »3» 55-38) Upper solar incisors of rats, on the molars of which one anti-caries effectiveness and inclusion at the same time of the fluorine in the tooth enamel from those to be examined Funds examined.

The cariesogenic activity of the plaque was determined

- lo -

with 15 volunteers (15 people in each group) according to the HardwicK method (Hardwick, Brit. dent. J., 1960, 108, 255-260). Before determining the caries ^ -en Activity of the dental plaque, it was recommended to these persons, not brushing teeth for 24 hours.

The inhibition of the acidic microflora of the dental plaque found in the same 45 volunteers, the tablets of known composition and tablets have taken composition according to the invention, in Samples of the dosed plaque by successive Dilutions of the starting material in the physiological solution, resulting in tolerant and elective liquid hazards and agar culture media for the vegetation of streptococci j

and lactobacteria obtained from samples of plaque j

be weeded out. The quantitative evaluation was carried out f

according to the titers of the microorganisms. '*:

The opson phagocytic index number of saliva and |

the content of lysozyme in saliva for determining the |

anti-inflammatory effect was found in 30 people with the I.

similar development of effects of the initial gingivitis <<

seeks. Some of them have tablets of known composition Settlement or the agent according to the invention a * '

taken. Assessment of the activity of inflammatory heai- ti

menden effect of the .Means, one led according to the well-known y

Methodology. Autostammen f was used as a test culture

of the golden-colored staphylococcus, which from the content of the *

ozyt 'Λ calculated for the opsonophagocytic index number

Periodontal pockets are discarded in the preparation spreads counted to the total number of phagocytosed * O

Microorganisms, and the arithmetic mean of one leukocyte each Λ

was holding. The activity of lysozyme, as an indicator of the ^l

Örtüohen state of the protection factors, we determined in the saliva mixed in 1.5-2 hours after breakfast in J ~ 't Radial diffusion method in agar Biphthalat. Lysozyme content r was expressed in ^ g / ml. The results of tests fjf are shown in Tables 5 and 6. ^

- 19 Table 5

transition α he active ingredients of the Tablets in the oral cavity fluid

Serial Designation of the no. Remedy for the teeth

Composition of the oral cavity sirekelt in m «/ l

Ionized fluorine

Hydrolyzable s pluor

Approx

The agent was not used (control) 0.03

207

Anticaries agents (Calcipot F) in tablet form of known composition

0.4

217

Inventive agent for teeth in the form of tablets

26.2

39.1

794 452

- 20 table 6

Comparative information on the properties of the anti-caries tablets of known composition (Calcipit-ϊ ¹ ) and the invented agent

Serial description Examined Permeabi Antik for 45 _Ca in 100 4th Indicators Acid resis- 6th No. . of the means lity of gigantic % in relation O Content of teziz d.Zann- 28.4 + 7.7 of the tooth fictitious on Kon j? in the melt melt activity in % trolls surfaces of rats 3 layer d. GRT test in 84.8 Enamel sec 12.4 zes in 55.2 + 5.1 Weight% 1 2 5 2 The middle Invention 59.7 0.074+ became moderate 55.2 0.0009 65, ^ + 1.8 not applied for teeth in turns tray (Control) ter shape 5 Tablets O, OO9-9t better known 0.0008 Together settlement (CaIoipot-F) 4th 0.0248+ 0.0009

Table 6 (cont.)

Examined indicators

Cariesogens
Effect of
Zaimbeläge
in people

Number of d. saureprod uz uzing the microorganisms d.

Opsono salary

phagocytic to lysozyme

see index in saliva, number in g / ml

ge in humans in saliva titers of humans

in unity

Streptococci

1O ~ ⁶ -1O " ⁷ lactobacteria

Γ ⁵ - 10 " ⁶ 2.5-3.0

10

190-195

Streptococci

ΙΟ " ⁴

Lactobacteria

10 ~ ⁵

1.9-2.2

180-186

+

Streptococci " ²

1.1-1.4

10
Lactobacteria

10 ~ ⁵ - 10 ^4180-195

U Ί Ö Z

The analysis of the results shows that the transition of the active ingredients of the tablets (fluoride compounds, phosphorus-calcium salts) Tablets according to the invention are made at concentrations which are 2-7 times higher than those used in anti-caries tablets of known composition, which ensures their significantly higher activity in the oral cavity. According to the action of five components of the tablets according to the invention. Medium, the permeability of the tooth enamel for 4-5 _c decreases by about 1.5 times, which prevents the penetration of harmful agents from the oral cavity into the solid tooth tissues and gives a strongly pronounced anti-caries effect (3 times higher than with tablets of known composition ). At the same time, the penetration of the active components of the composition itself, especially fluorine, is increased by 2.5 times and the acid resistance by! The cariesogenic activity of the dental plaque is reduced to a minimum, which is due to the lowering of the titer of the acid-producing ivlikroflora. The index number of anti-inflammatory activity (opsonophagocytic index number) approaches the normal physiological level in the persons who have taken the tablets of the composition according to the invention. Here, the Paktor the natural Scnutzas is not suppressed, a sign is the high reference of the content of Ly sozym in Speiohel. . ■ "'

The medicament according to the invention in the form of tablets

. or coated tablets are produced in a manner known per se posed.

3P The anti-caries substance used in the composition of the drug is prepared as follows.

ί The bone tissue · is diluted with mineral acid, in particular Pour hydrochloric acid over it and immerse it in the dilute mineral acid while mixing until the mineral acid is completely dissolved Components and water-soluble proteins that are present in bone tissue are kept.

Then the prepared solution is separated and washed with water with the addition of a stabilizing agent, lemon

acid beüieiiun ^ evue iye of their salts, diluted, after which i; .an the Solution neutralized.

• To guarantee the conditions of transport and for storage, the iJtoff is produced in dry form. With this aim, the solution is sprayed in a drying system.

The product made is a white amorphous powder with no odor with a slightly salty taste, it is easily soluble in water, is very little soluble in 95% alcohol and practically insoluble in ester.

The agent according to the invention is administered orally in one dose (in grams): N atr i ummonof 1 uor opho sphat 0.0065-0.0075, .Anticaria s st off 0.16-0.18, once a day for 250 days taken. When taken orally, it is desirable to chew the preparation according to the invention. The inventive Medium has no contraindications and side effects.

Claims (3)

Uf :! > v I M I ■> I TJ ι, M Λ t I V-. I- INC. K /. ; I -j ι Λ ι, .-. / ■ ι 1 II ι · H <■ I · I /. t. I 'Λ 1 IN 1 Λ I 1 (J li N f. "Y ! -> '. "/» L-l Λ Mil I IM ΛΙ / VAH. MUMC HI M' K) I · 1 ·. '. i / -I JWI ". ·.! l '() i, ll" ÄC.H ΊΙιΙΙΚ, Ο. O- Hf) DtI MUNCHLN 'Ib RISKY MEDICINKY INSTITUTE Central'nyj naucno-issledovatel'skij
institut stomatologii DEAA-30783.5 March 21, 1983 ZUR BSHAIiDLUi ¹ JG DaR IiARIBb DIA Z) IHFiS ^ PATENT CLAIM: 1, przne inimittel for the treatment of tooth decay, that eii ^ e / Vv'irkstoi'f and a pharmaceutical diluent provides, characterized in that that the active ingredient is a mixture of Natrimnuionofluorophosphat and contains anti-caries, which is a product by processing the bone tissue with a diluted mineral acid until it is completely dissolved the mineral components and the water-soluble SiW substances contained in the bone tissue Separation of the prepared solution, its dilution with 7 / water with the addition of a stabilizing agent, citric acid or their salts, and subsequent neutralization and drying of the solution is prepared and the following components in% by weight has: Calcium 2-6 Sodium 19-22 Potassium. 0.04-0.18 Anion of mineral acid (chloride) 6-10.6 Anion of orthophosphoric acid 1.3-5.0 water-soluble proteins 1.0-5.0 ..ladies ium 0.0 ^ -0.2 ^^ Complex of trace elements including Pluor, manganese, tin, zinc and iron 0.01-0.02 complex Citratν erb indungen to ^ alculated to an anion of citric acid all the rest at the following ratio of the "Virkstoffes zam pharmaceutical diluent 1:25» 5-1: 24.5. 2. Medicament according to claim 1 in tablet form, characterized in that it is oen Active ingredient in grams One! Tablet each contains: Sodium monofluorophosphate - 0.0065-0.0075 Anti-caries - 0.16-0.18. 3. Medicament according to claim 1 and 2 in tablet form, by -fc-e denotes that it as a pharmaceutical diluent, a pharmaceutical one Contains filler, starch and lactose.