CN1158249A - Preparation for oral cavity medicine - Google Patents

Abstract

A medicine in the form of paste, liquid and film for oral cavity is prepared from active components such as metronidazole and chlorhexidine acetate, and medicinal carrier including glycerine, carboxymethylcellulose, calcium hydrogen phosphate, sodium saccharin, sodium pyrophasphate, sodium dodecylol sulfate and spearmint essence. Its preparing process is disclosed.

Description

Medicine preparation for oral cavity

The present invention relates to a kind of medicine preparation for oral cavity.

Periodontal disease is to cause that the tooth disease undermines the principal disease of disappearance.Treatment periodontal disease medicine such as Metric 21 commonly used at present, this medicine has certain curative effect, but because be oral, the side effect of whole body is bigger, therefore can not use over a long time.In addition, periodontal disease is a kind of chronic disease, is easy to fall ill repeatedly, and treatment is brought certain difficulty.

The objective of the invention is to overcome above-mentioned shortcoming, develop a kind of new medicine preparation for oral cavity, it can directly act on the oral cavity disease sites, and the patient can make things convenient for medication.And the difficult drug resistance that produces.

The invention provides a kind of medicine preparation for oral cavity (having another name called periodontal No. one).

Medicine preparation for oral cavity of the present invention is made up of as active ingredient and pharmaceutical carrier metronidazole and chlorhexidine acetate, and forms 100% composition to contain active ingredient 0.06-1.3% (weight %) with the arbitrary proportion that contains medicinal carrier 99.4-98.7% (weight %).Active ingredient metronidazole content is 0.05-0.8% (weight %), and chlorhexidine acetate content is 0.01-0.5% (weight %), and metronidazole can mix use with arbitrary proportion with chlorhexidine acetate in above-mentioned scope.It is 12-30%, binding agent such as carboxymethyl cellulose or hydroxypropyl methylcellulose that pharmaceutical carrier has wetting agent such as glycerol, sorbitol or polyhydric alcohol equal size.Content is 0.5-1.6%, abrasivus such as calcium hydrogen phosphate.Aluminium hydroxide, calcium carbonate or silicon dioxide equal size are 25-50%, correctives such as saccharin sodium or sweet close element, content be 0.1-0.3%, antioxidant such as tetrasodium pyrophosphate or pyrophosphorous acid sodium content be the smart content of 0.05-0.8%, spice such as Herba Menthae Rotundifoliae for for 0.1-2%, surfactant such as sodium lauryl sulfate or Tween 80 content be 0.2-2.5%, aromatic such as Oleum menthae contain for 0.05-0.5%, coloring agent be that polyvidone, solvent are ethanol or distilled water for U.S. blue, film former.

It is as follows that medicine preparation for oral cavity of the present invention (No. one toothpaste of periodontal) is made antibacterial testing result through Shanghai Medical Univ: one, sample title: 1, No. 1 toothpaste of periodontal (sample 1) 2, No. 1 toothpaste of periodontal (sample 2) are got after depositing in 1 year

Sample.

3, blank toothpaste two, detection method:

With the anaerobism isolation medium dry powder that Shanghai Vaccine and Serum Institute produces, by specification is dissolved in water and adds the vitamin K1 autoclaving, is cooled to 50 ℃, adds the 5-10% Sanguis caprae seu ovis again, shakes up and pours the sterilization plate into, (thickness is 6mm).The a certain bacterial strain of every plate intensive streak inoculation in surface.With the broken pipe of the sterilization of diameter 6mm, on flat board, punch then, cut out agar.In the hole, amount of paste is put into anaerobic jar then and is detested 48-72 hour (37 ℃) of bacterium cultivation with proper surperficial equal with agar plate with the careful toothpaste that injects of syringe.Observe.Measure diameter with antibacterial ring around the record toothpaste.Three, testing result:

3 kinds of toothpaste of table 1 are to 4 kinds of anaerobe bacteriostasis

(inhibition zone diameter, millimeter mm) No. 1 toothpaste of the blank No. 1 toothpaste periodontal of toothpaste periodontal of strain

(sample 1) (sample 2) bacteroides melaninogenicus 19 51 49 gingiva bacteroids 18 53 (45-60) 45 nuclear Fusobacteriums 14 55 53 actinomyces viscosus 13 22 20

Show that from experiment medicine preparation for oral cavity of the present invention has significant inhibitory effect to the anaerobe that causes odontopathy (mainly being periodontal disease).

The toxicity test that medicine preparation for oral cavity of the present invention (No. one, periodontal) is done through institute of materia medica, Chinese Academy of Sciences Shanghai is reported as follows: sample title: No. one toxicity test project of periodontal: irritate stomach (ig) acute toxicity test in mice (LD ₅₀Test) material and method: laboratory animal, 40 of Kunming kind white mice, body weight 18-22g, male and female half and half, every Mus is irritated stomach (lg) respectively and awards No. one 0.7ml of periodontal and (be equivalent to 35g/kg.Observed for two weeks after the administration.Experimental result: 40 mouse stomaches award periodontal No. one, observe there is no poisoning symptom or death through two weeks, and mice is movable normal, press medicine toxicity grading standard, allly all belong to nontoxic grade of material greater than 5g/kg.

The animal safety pharmacological testing that medicine preparation for oral cavity of the present invention (No. one, periodontal) is done through institute of materia medica, Chinese Academy of Sciences Shanghai is reported as follows: sample title: No. one toxicity test project of periodontal: animal safety test material and the method that No. one, periodontal: laboratory animal, Kunming kind white mice, body weight 18-22g, male and female half and half, totally 32, be divided into test specimen group and matched group, 16 every group, No. one 25g/kg of test specimen group mouse stomach (lg) periodontal, matched group ig normal saline 0.5ml.Mice was weighed once in per 3 days, and nominal 6 times was observed 15 days.Experimental result: 1,16 mices of test specimen group all survive.

2,16 mice body weight of test specimen group are the same with matched group is normal

Increase (seeing Table).

The safety pharmacological tests that No. one, table 2 periodontal

Every Mus average weight (gram)	Body weight before irritating	Body weight behind the filling stomach
							The same day	The 3rd day	The 6th day	The 9th day	The 12nd day	The 15th day
	Sample sets 25g/kg	????20.2	????21.3	????24.2	???27.7	????31.0							????33.1
Matched group							????19.9	????23.4	????26.3	???29.9	????32.4	????33.9

Medicine preparation for oral cavity of the present invention (No. one, periodontal) is as follows through clinical observation result:

Case is selected: select not use as yet among the outpatient gingivitis, patients with periodontitis 100 examples of any Drug therapy at random, give periodontal No. one, and carry out tracing study.

Administrated method: early, middle and late totally 3 times (at least 2 times) each 3 minutes of brushing teeth every day, the back further consultation of two weeks.

Clinical indexes:, must before and after treatment, write down the following index respectively to using the patient of No. one, periodontal.

(1) plaque index: 0-does not have bacterial plaque; The facing in the nearly gum edge of 1-district has thin bacterial plaque; The bacterial plaque of visible gum edge of 2-naked eyes or proximal surface moderate; 3-gum edge or facing have a large amount of soft dirts and bacterial plaque.

(2) gingival index: 0-gingiva mild hyperaemia, edema, spy is examined not hemorrhage; 2-gingiva moderate inflammation, rubescent, edema, gum surface are shinny, visit examine hemorrhage; 3-gingiva hyperphlogosis has obvious redness, edema, ulcer, and automatic bleeding tendency is arranged.

(3) sulcular bleeding index: 0-is not hemorrhage; 1-is hemorrhage when gently visiting gingival sulcus, and the gum outward appearance is normal; 2-is hemorrhage when visiting gingival sulcus, and gingiva reddens, no swelling; The 3-gingiva has ulcer or other symptoms.

Table 3 therapeutic evaluation

Project	The example number		Effective percentage (%)
				Constant	Reduce
	Plaque index changes gingival index and changes the bleeding index variation	????21 ????20 ????9				????79 ????80 ????91	????79 ????80 ????91

Relatively 100 routine patients use the symptom of No. one front and back of periodontal, and three are detected indexs and show all and take a favorable turn that the effective percentage that periodontal reduces bacterial plaque for No. one is 79%, and the effective percentage that controls inflammation is 80%, and it is hemorrhage particularly remarkable to reduce gingival sulcus, and effective percentage reaches 91%.No. one, periodontal is evident in efficacy to symptoms such as gingivitis, periodontitis, gingival hemorrhages, and untoward reaction is not found in clinical use one year over thereby as seen.

Medicine preparation for oral cavity of the present invention can have multiple dosage forms such as paste, membrane and water preparation.

The quality standard of medicine preparation for oral cavity of the present invention is as follows: 1, differentiate: get this product 20 gram adding distil water 50ml fully stir evenly in water-bath warm, filtered while hot, filtrate is concentrated into about 10ml, hydro-oxidation sodium test solution 2ml is warm, promptly gets purplish red solution; Drip dilute hydrochloric acid and make that to be acidity be yellowing, drip the excessive sodium hydrate test solution again, then become orange red.Be the metronidazole positive reaction.2, assay: get about 5 grams of this product, the accurate title, decide, and adds hydrochloric acid solution (0.1mol/L), fully dissolving, and tepor glass filter (G4) filters.Measure trap at the UV277nm place.

Medicine preparation for oral cavity of the present invention has good restraining and killing action to the malignant bacteria of periodontal disease, evident in efficacy to symptoms such as gingivitis, periodontitis, gingival hemorrhage, gingival swelling and pain, halitosiss, can the part be coated with or brush teeth, gargle etc., the each 1-2 gram of consumption has no adverse reaction, and dosage is little, can play a role in the part rapidly after the use, not producing drug resistance, and can use repeatedly on demand, is a kind of good stability, cheap oral cavity medicine novel formulation.

Another object of the present invention provides the preparation method of a kind of medicine preparation for oral cavity of the present invention (No. one, periodontal).This method is that correctives and antioxidant mixing are dissolved in the distilled water of 1/2 formula ratio, metronidazole and chlorhexidine acetate is mixed in the warm distilled water that is dissolved in 1/2 formula ratio (70-80 ℃ of water temperature) again, merges two liquid; Taking adhesive is dispersed on the wetting agent liquid level in addition, then above-mentioned merging solution is poured in this wetting agent, constantly stirs, and it is expanded evenly, adds abrasivus more successively, and spice, surfactant constantly stir, grind, last vacuum outgas packing.

Preparation method of the present invention is simple and easy to do, is suitable for the suitability for industrialized production of scale.

No. one paste of example 1 preparation periodontal 60 grams

Composition weight (%)

Metronidazole 0.06

Chlorhexidine acetate 0.2

Glycerol 12

Carboxymethyl cellulose 0.8

Calcium hydrogen phosphate 20

Saccharin sodium 0.1

Tetrasodium pyrophosphate 0.5

Herba Menthae Rotundifoliae essence 0.8

Sodium lauryl sulfate 1.8

Distilled water adds to the 100ml method: by above-mentioned prescription saccharin sodium, tetrasodium pyrophosphate are dissolved in an amount of distilled water, other gets metronidazole, chlorhexidine acetate is dissolved in an amount of hot distilled water, merges two liquid then.Carboxymethyl cellulose is dispersed on the glycerol liquid level, then above-mentioned aqueous solution is joined to go in the glycerin liquid to make and expand evenly, constantly stir, add calcium hydrogen phosphate, essence, sodium lauryl sulfate more successively, constantly stir, grind the vacuum outgas packing.No. one paste of example 2 preparation periodontals 60 grams

Composition weight (%)

Metronidazole 0.1

Chlorhexidine acetate 0.04

Glycerol 15

Carboxymethyl cellulose 1.0

Calcium hydrogen phosphate 25

Saccharin sodium 0.12

Tetrasodium pyrophosphate 0.5

Herba Menthae Rotundifoliae essence 1.0

Sodium lauryl sulfate 2.0

Distilled water adds to 100ml

Method is with example 1.No. one paste of example 3 preparation periodontals

Composition weight (%)

Metronidazole 0.4

Chlorhexidine acetate 0.01

Glycerol 18

Carboxymethyl cellulose 1.2

Calcium hydrogen phosphate 40

Saccharin sodium 0.14

Tetrasodium pyrophosphate 0.5

Herba Menthae Rotundifoliae essence 1.2

Sodium lauryl sulfate 2.2

Distilled water adds to 100ml

Method is with example 1.No. one rinse liquid of example 4 preparation periodontals

Composition weight (%)

Metronidazole 0.05

Chlorhexidine acetate 0.01

Oleum menthae 0.05

Tween 80 0.05

Saccharin sodium 0.05

Ethanol 1.2

U.S. blue an amount of

Distilled water adds to 100ml

Method: get distilled water 80ml and be heated to 80 ℃, add metronidazole, chlorhexidine acetate and saccharin sodium and make its dissolving, other gets Oleum menthae, Tween 80 adds in the ethanol, mix homogeneously, and two liquid merge, and filter, and add an amount of U.S. orchid and distilled water to 100ml.No. one rinse liquid of example 5 preparation periodontals

Composition weight (%)

Metronidazole 0.8

Chlorhexidine acetate 0.5

Oleum menthae 0.5

Tween 80 0.5

Saccharin sodium 0.2

Ethanol 24

U.S. blue an amount of

Distilled water adds to 100ml

Method is with example 4.

No. one membrane of example 6 preparation periodontals

Composition weight (%)

Metronidazole 0.05

Chlorhexidine acetate 0.01

Saccharin sodium 0.05

Polyvidone is an amount of

Distilled water adds to 100ml

Method: get distilled water 50ml and be heated to 80 ℃, add metronidazole, chlorhexidine acetate and saccharin sodium and make its dissolving, polyvidone is dissolved in the distilled water, two liquid are evenly mixed then, and distilled water adds to 100ml.

No. one membrane of example 7 preparation periodontals

Composition weight (%)

Metronidazole 0.8

Chlorhexidine acetate 0.5

Saccharin sodium 0.2

Polyvidone is an amount of

Distilled water adds to 100ml

Method is with example 6.

Claims (4)

1, a kind of medicine preparation for oral cavity (No. one, periodontal), it is characterized in that said preparation is made up of as active ingredient and pharmaceutical carrier metronidazole and chlorhexidine acetate, and can form 100% composition with the arbitrary proportion that contains medicinal carrier 99.4-98.7% (weight %) by containing active ingredient 0.06-1.3% (weight %), wherein the content of active ingredient metronidazole is 0.05-0.8% (weight %), chlorhexidine acetate content is 0.01-0.5% (weight %), and metronidazole can mix use with arbitrary proportion with chlorhexidine acetate in above-mentioned scope.

2, medicine preparation for oral cavity according to claim 1 (No. one, periodontal) is characterized in that wherein said pharmaceutical carrier has wetting agent glycerol, sorbitol or polyhydric alcohol content are 12-30% (weight %), binding agent carboxymethyl cellulose or hydroxypropyl methylcellulose content are 0.5-1.6% (weight %), the abrasivus calcium hydrogen phosphate, aluminium hydroxide, calcium carbonate or dioxide-containing silica are 25-50% (weight %), tender flavor agent saccharin sodium or sweet close cellulose content are 0.1-0.3% (weight %), antioxidant tetrasodium pyrophosphate or pyrophosphorous acid sodium content are 0.05-0.8 (weight %), the smart content of spice Herba Menthae Rotundifoliae is 0.1-2% (weight %), surfactant sodium lauryl sulfate or Tween 80 content are 0.2-2.5% (weight %), aromatic Oleum menthae content is 0.05-0.5%, coloring agent is U.S. blue, film former is a polyvidone, solvent is ethanol or distilled water.

3, the preparation method of a kind of medicine preparation for oral cavity as claimed in claim 1 (No. one, periodontal), it is characterized in that this method is that correctives and antioxidant mixing are dissolved in the distilled water of 1/2 formula ratio, again metronidazole and chlorhexidine acetate are mixed in the warm distilled water that is dissolved in 1/2 formula ratio (70-80 ℃ of water temperature), merge two liquid; Taking adhesive is dispersed on the wetting agent liquid level in addition, then above-mentioned merging solution example is gone in this wetting agent, constantly stirs it is expanded evenly, adds abrasivus, spice, surfactant more successively, constantly stirs, grinds, last vacuum outgas packing.

4, medicine preparation for oral cavity according to claim 1 (No. one, periodontal) is characterized in that said preparation has paste, water preparation and membrane.