CN107281360A - A kind of Chinese medicine composition, preparation and preparation method for treating halitosis - Google Patents
A kind of Chinese medicine composition, preparation and preparation method for treating halitosis Download PDFInfo
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Abstract
The invention provides a kind of Chinese medicine composition for treating halitosis, preparation and preparation method thereof, Chinese medicine composition is made up of Chinese medicine radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, dried orange peel, said composition can suppress the growth of halitosis pathogenic bacteria, and the present composition can directly pulverize mixing or the active component that is extracted by this area conventional extraction techniques combines with pharmaceutically acceptable pharmaceutic adjuvant and various pharmaceutical dosage forms are made；It may also be fabricated which that the present composition and preparation can improve halitosis, evident in efficacy containing buccal tablet.
Description
Technical field
The invention belongs to tcm field, and in particular to a kind of Chinese medicine composition, preparation and preparation method for treating halitosis.
Background technology
Halitosis (oralmalodororhalitosis) refers to a kind of symptom that peculiar smell is given out during breathing, old in being apt to occur in
Year people.Halitosis not only influences the normal social interaction of resident, is also the principal element for causing mental handicape.The whole world is about according to investigations
The people for having 1/4 suffers from different degrees of halitosis.The origin cause of formation of halitosis is divided into external cause and internal cause, and external cause has smoking, drinks or feed
Garlic, onion etc. have penetrating odor food or other excitant condiment, are directly stinked from oral cavity and alimentary canal, internal cause is then
It is due to that oral cavity or gastrointestinal system disease cause.For modern medicine angle, halitosis is broadly divided into three types：Mouth source property
Halitosis, is often to be caused by various gum diseases or oral hygiene situation are bad；Non- mouth source property halitosis, is often exhaled by various
What desorption system and digestive system infection triggered；Spirituality halitosis, the type halitosis only patient can smell oneself.High by 80% according to statistics~
90% halitosis is that microbial metabolism is produced in oral cavity.Mouthful source property halitosis be due to oral cavity cause smelly bacterium will by protein and
The amino acid that many hydrolase polypeptides are formed, mainly sulfur-containing amino acid (cysteine, cystine and methionine) are degraded into vulcanize
Volatile gaseous compound (VSC) based on hydrogen, methyl mercaptan and diethyl sulfide, the oral peculiar smell formed by.
The treatment for halitosis, which concentrates on suppression, at present can produce volatile sulfur compounds (VSC) bacterium, clinically many
Using the chemicals or chemical gargle of anaerobe resistant, short term effect is fine, but side effect is big, and bacterial drug resistance constantly increases
By force, long-term effect is not good.China's Chinese medicine has toxicity low, and Small side effects, drug resistance is low, the advantage such as resource is wide, anti-in halitosis
Controlling the exploitation of aspect has extensive prospect, therefore according to the change of current natural society's environment, works out the current disease of adaptation
That embodies can effectively prevent that the Chinese prescription of halitosis is extremely important.
The content of the invention
To solve the above problems, the invention provides a kind of Chinese medicine composition for treating halitosis, by weight, by crown prince
87-119 parts of ginseng, 61-94 parts of Chinese yam, 20-46 parts of the dried rhizome of rehmannia, 38-62 parts of the red sage root, 59-88 parts of dark plum, 35-60 parts of the banksia rose, wrinkled giant hyssop
19-35 parts, 22-47 parts of the root of Dahurain angelica, 8-19 parts of grass-leaved sweetflag, 10-23 parts of dried orange peel be made.
Specifically：The invention provides a kind of Chinese medicine composition for treating halitosis, by weight, by radix pseudostellariae 98-110
It is part, 70-81 parts of Chinese yam, 28-37 parts of the dried rhizome of rehmannia, 47-54 parts of the red sage root, 70-77 parts of dark plum, 42-50 parts of the banksia rose, 26-30 parts of wrinkled giant hyssop, white
30-39 parts of the root of Dahurian angelica, 12-16 parts of grass-leaved sweetflag, 15-19 parts of dried orange peel are made.
More specifically, the invention provides a kind of Chinese medicine composition for treating halitosis, by weight, by radix pseudostellariae 101
Part, 76 parts of Chinese yam, 33 parts of the dried rhizome of rehmannia, 51 parts of the red sage root, 74 parts of dark plum, 46 parts of the banksia rose, 28 parts of wrinkled giant hyssop, 35 parts of the root of Dahurain angelica, 14 parts of grass-leaved sweetflag,
17 parts of dried orange peel is made.
Composition of the present invention, which can directly pulverize, to be mixed or is extracted by this area conventional extraction techniques
Various pharmaceutical dosage forms are made with pharmaceutically acceptable pharmaceutic adjuvant in the active component gone out.
Described excipient substance can for sweetener, acid, preservative, wetting agent, lubricant, wetting agent, disintegrant,
Diluent and adhesive.
Present invention also offers a kind of preparation method for the Chinese medicine composition for treating halitosis, comprise the following steps：
Radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs are taken through water extraction
Method is decocted twice, and the water of total 10 times of medicinal material amount is added for the first time, is decocted 2 hours, and 200 mesh filtering reserved filtrate is standby, adds for the second time
The decocting for entering 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, merges filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relative density and is
The thick paste of (1.05-1.30 60 DEG C)；Various pharmaceutical dosage forms are made with pharmaceutically acceptable pharmaceutic adjuvant in thick paste again.
Described pharmaceutical dosage form is buccal tablet, spray, tea bag.
Present invention also offers a kind of preparation method for the buccal tablet for treating halitosis, comprise the following steps：
Reduced vacuum is dried under the conditions of taking thick paste, 40-60 DEG C, and dry cream crushed 100 mesh sieves；Take 35-55 parts of PVPs
It is well mixed after K30,300-350 portions of mannitol, granulation, after 40-60 DEG C of drying, whole grain adds 14-26 parts of magnesium stearates,
Well mixed, tabletting obtains buccal tablet.
Further, the preparation method of the buccal tablet of described treatment halitosis, comprises the following steps：
Reduced vacuum is dried under the conditions of taking thick paste, 50 DEG C, and dry cream crushed 100 mesh sieves；Take 45 parts of PVP K30s, 325 parts
It is well mixed, granulation, after 50 DEG C of dryings, whole grain adds 20 parts of magnesium stearates, is well mixed, tabletting must be sucked after mannitol
Piece.
The principle and beneficial effect of the present invention is：
Radix pseudostellariae：For pinkwort caryophyllaceous ginseng (Pseudostellaria heterophylla (Miq.) Pax ex
Pax et Hoffm.) dried root；It is sweet, slight bitter, tepor；Help spleen and lung, nourishing generate fluid.
Chinese yam：For Dioscoreaceae plant Chinese yam Dioscorea opposita Thunb. dry rhizome；It is sweet, put down；Tonifying spleen is supported
Stomach, engender liquid and benefic lung, the puckery essence of kidney tonifying.
The dried rhizome of rehmannia：For scrophulariaceae rehmannia glutinosa plant Rehmannia glutinosa Libosch. fresh or dried root；It is sweet,
It is cold；Clearing heat and cooling blood, yin-nourishing is promoted the production of body fluid.
The red sage root：For labiate red sage root Salvia miltiorrhiza Bunge. drying root and rhizome；Hardship, it is micro-
It is cold；Stasis-dispelling and pain-killing, invigorate blood circulation, relieving restlessness that clears away heart-fire.
Dark plum：For rose department plant plum Prunus mume (Sieh.) Sieb.et Zucc. drying almost ripe fruit；
It is sour, puckery, put down；Astringe the lung, puckery intestines promote the production of body fluid, claming ascaris.
The banksia rose：For feverfew banksia rose Aucklandia lappa Decne. dry root；Pungent, hardship, temperature；Promoting qi circulation and relieving pain,
Reinforcing spleen to promote digestion.
Wrinkled giant hyssop：For labiate Pogostemon cablin or the herb of wrinkled giant hyssop；It is pungent, tepor；Fast gas, and in, ward off dirty, clearing damp.
The root of Dahurain angelica：For umbellate form section the plant root of Dahurain angelica Angelica dahurica (Fisch.ex Hoffm.) Benth.et
Or Radix angelicae dahuricae Angelica dahurica (Fisch.ex Hoffm.) Benth.et Hook.f.
Hook.f.var.formosana (Boiss.) Shan et Yuan dry root；It is pungent, temperature；Dissipate wind dehumidifying, sensible analgesic, detumescence
Apocenosis.
Grass-leaved sweetflag：For acorus gramineus araceae plant Acorus tatarinowii Schott dry rhizome；Pungent, hardship,
Temperature；Dampness elimination appetizing, slit phlegm of having one's ideas straightened out, inducing resuscitation intelligence development.
Dried orange peel：For rutaceae orange Citrus reticulata Blanco and its drying and ripening of variety fruit
Skin；It is bitter, pungent, temperature；Regulating qi-flowing for strengthening spleen is eliminating dampness and eliminating phlegm.
Chinese medicine composition of the present invention is by radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, old
Skin is constituted, and the radix pseudostellariae thoughts of returning home, spleen, lung three pass through, and is replenished qi to invigorate the spleen, promoting production of body fluid and nourishing the lung, Chinese yam returns spleen, lung, kidney channel, invigorating the spleen, tonifying lung, Gu
Kidney, strengthening the essence, qi-restoratives, clearind deficient heat, the dried rhizome of rehmannia thoughts of returning home, liver and kidney channel, heat-clearing, the red sage root thoughts of returning home, Liver Channel, promoting blood circulation, calming heart and tranquilizing mind, row
Purulence, analgesic, dark plum enter liver, spleen, lung, large intestine channel astringe the lung to stop cough；Relieving diarrhea with astringents；Hemostasis is promoted the production of body fluid, and the banksia rose enters lung, liver, the spleen channel, temperature
Stomach is neutralized, wrinkled giant hyssop enters lung, spleen, stomach, driving away summer heat inducing diaphoresis；Removing dampness to restore normal functioning of the stomach, the root of Dahurain angelica enters lung, thigh, stomach, dispels pathogenic wind and remove dampness, swelling and pain relieving,
The grass-leaved sweetflag thoughts of returning home, stomach, dissipating phlegm for resuscitation, dampness elimination promoting the circulation of qi, dried orange peel return lung, the spleen channel.Prescription of the present invention is of a tightly knit structure, scientific and reasonable,
The banksia rose, dried orange peel are qi-regulating drug, with the effect dredged mechanism of qi, eliminate the stagnation of the circulation of vital energy, the pancake circulation of vital energy in the wrong direction, and the root of Dahurain angelica has the effect of inducing diaphoresis, dissipates
Table is evil, and radix pseudostellariae, Chinese yam are qi-restoratives medicine, and help healthy tendency, raising immunity, the dried rhizome of rehmannia have the effect of clearing heat and cooling blood, and wrinkled giant hyssop dampness elimination is changed
Dehumidifying is turbid, and happy taste of waking up, the red sage root has promoting blood circulation, promotion blood, the effect of dissipation hemostasis, and grass-leaved sweetflag has sensible switching function,
Dark plum restrains astringent or styptic treatment for spontaneous sweating, each mutually coordinated effect of taste Chinese medicine, mild in medicine property and copolymerization damp and clearing heat, the effect of strengthening the spleen and stomach.
Chinese prescription of the present invention is by the research of substantial amounts of prescription and screening experiment, it is determined that with radix pseudostellariae, Chinese yam, life
Ground, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, dried orange peel are composition, and composition is made into buccal tablet, smell delicate fragrance,
Dampness elimination heat-clearing, strengthening the spleen and stomach, build up health, and suppress the growth of halitosis pathogenic bacteria, significant curative effect is respectively provided with to all kinds of halitosis.
Preferably to illustrate beneficial effects of the present invention, the present invention has also listed following test example, it is intended to illustrate this hair
Bright beneficial effect, but it is by no means limited to protection scope of the present invention.
The present composition of experimental example 1 is to halitosis pathogenic bacteria antibacterial experiment in vitro
1.1 test strain
Porphyromonas gingivalis (Pg), Fusobacterium nucleatum (Fn)
1.2 trial drugs and packet
Test group 1：By radix pseudostellariae 80g, Chinese yam 55g, dried rhizome of rehmannia 18g, red sage root 35g, dark plum 55g, banksia rose 30g, wrinkled giant hyssop 15g
Thick paste made from part, 18g parts of the root of Dahurain angelica, 7g parts of grass-leaved sweetflag, dried orange peel 8g；(low component)
Test group 2：By radix pseudostellariae 87g, Chinese yam 61g, dried rhizome of rehmannia 20g, red sage root 38g, dark plum 59g, banksia rose 35g, wrinkled giant hyssop 19g,
Root of Dahurain angelica 22g, grass-leaved sweetflag 8g, thick paste made from dried orange peel 10g；
Test group 3：By radix pseudostellariae 98g, Chinese yam 70g, dried rhizome of rehmannia 28g, red sage root 47g, dark plum 70g, banksia rose 42g, wrinkled giant hyssop 26g,
Root of Dahurain angelica 30g, grass-leaved sweetflag 12g, thick paste made from dried orange peel 15g；
Test group 4：By radix pseudostellariae 101g, Chinese yam 76g, dried rhizome of rehmannia 33g, red sage root 51g, dark plum 74g, banksia rose 46g, wrinkled giant hyssop 28g,
Root of Dahurain angelica 35g, grass-leaved sweetflag 14g, thick paste made from dried orange peel 17g；
Test group 5：By radix pseudostellariae 110g, Chinese yam 81g, dried rhizome of rehmannia 37g, red sage root 54g, dark plum 77g, banksia rose 50g, wrinkled giant hyssop 30g,
Root of Dahurain angelica 39g, grass-leaved sweetflag 16g, thick paste made from dried orange peel 19g；
Test group 6：By radix pseudostellariae 119g, Chinese yam 94g, dried rhizome of rehmannia 46g, red sage root 62g, dark plum 88g, banksia rose 60g, wrinkled giant hyssop 35g,
Root of Dahurain angelica 47g, grass-leaved sweetflag 19g, thick paste made from dried orange peel 23g；
Test group 7：By radix pseudostellariae 122g, Chinese yam 98g, dried rhizome of rehmannia 50g, red sage root 68g, dark plum 92g, banksia rose 65g, wrinkled giant hyssop 40g,
Root of Dahurain angelica 50g, grass-leaved sweetflag 23g, thick paste made from dried orange peel 28g；(high component)
Control group：Not drug containing.
1.3 test method
Strain culturing：Recovery 48h 2 kinds of bacterium are seeded in BHI fluid nutrient mediums, 37 DEG C of Anaerobic culturels (80%N2,
10%CO2,10%H2) 24h, collects above-mentioned bacterium, bacterial solution concentration is adjusted to 1 × 108CFU/mL is standby, and each group is tried
Test a group medicine and take and mixed respectively with Fn, Pg bacterium solution in right amount, the nutrient solution of 37 DEG C of Anaerobic culturels 48h, 2mL not drug containing is used as control
Culture 10 is serially diluted to 10 again after the completion of group, culture-3~10-12Times, each dilution μ L of bacterium solution 50 are drawn, triangle glass is used
Push rod spread plate (BHI blood agar plates), 37 DEG C of Anaerobic culturel 3d in anaerobic culture box, according to the various bacterium of colonial morphology meter
CFU (CFU/mL).It is repeated 3 times and averages.
1.4 experimental result
Table 1：The present composition is to halitosis pathogenic bacteria antibacterial experiment in vitro (lgCFUmL-1, x ± s)
| Group | Porphyromonas gingivalis (Pg) | Fusobacterium nucleatum (Fn) |
| Control group | 16.12±0.10 | 15.38±0.07 |
| Test group 1 | 13.74±0.26 | 13.57±0.28 |
| Test group 2 | 13.50±0.13 | 13.36±0.24 |
| Test group 3 | 13.27±0.11 | 13.23±0.18 |
| Test group 4 | 13.01±0.06 | 13.14±0.10 |
| Test group 5 | 13.14±0.08 | 13.20±0.15 |
| Test group 6 | 13.21±0.09 | 13.26±0.21 |
| Test group 7 | 13.48±0.12 | 13.38±0.35 |
As can be seen from the above table, test group 2-6 is compared with control group, porphyromonas gingivalis (Pg) and Fusobacterium nucleatum
(Fn) bacterium amount significantly reduces (P<0.05), show test group 2-6 to halitosis pathogenic bacteria porphyromonas gingivalis (Pg) and tool core
Fusobacterium (Fn) has significant inhibitory action, and wherein preferably, test group 1 is low component, fungistatic effect to the fungistatic effect of test group 4
Poor, test group 7 is high component, and fungistatic effect is also slightly reduced, therefore, and the Chinese medicine composition of present invention treatment halitosis is preferably matched somebody with somebody
Than for：87-119 parts of radix pseudostellariae, 61-94 parts of Chinese yam, 20-46 parts of the dried rhizome of rehmannia, 38-62 parts of the red sage root, 59-88 parts of dark plum, banksia rose 35-60
Part, 19-35 parts of wrinkled giant hyssop, 22-47 parts of the root of Dahurain angelica, 8-19 parts of grass-leaved sweetflag, 10-23 parts of dried orange peel, optimal proportion is：101 parts of radix pseudostellariae, mountain
76 parts of medicine, 33 parts of the dried rhizome of rehmannia, 51 parts of the red sage root, 74 parts of dark plum, 46 parts of the banksia rose, 28 parts of wrinkled giant hyssop, 35 parts of the root of Dahurain angelica, 14 parts of grass-leaved sweetflag, dried orange peel
17 parts.
The present composition lanqin oral solutions of experimental example 2
Experimental subjects：With serious halitosis symptom totally 60, age 35-70 Sui, wherein women 25, male 35.
Experimental method：Experimental subjects is divided into test group, blank group and control group, every group of 20 people；
Test group：The lozenge that the embodiment of the present invention 6 is prepared is tasked experimental subjects and used, and application method is；Daily 1
Piece, three times a day, divides and uses in the morning, afternoon and evening.
Blank group：It is without any processing.
Control group：Pepper mint eucalyptus lozenge (I) (Green's pharmacy) is used to experimental subjects, it is buccal, contained 1 every 0.5~1 hour
Piece.
Experimental result is shown in Table 2.
Table 4：Lozenge clinical tests situation table (counting per capita) produced by the present invention
As can be seen from the above table, control group and test group can significantly improve experimental subjects halitosis compared with blank group
Symptom (P<0.05) it is, and test group is compared compared with control group, better efficacy, efficient up to 95%, show produced by the present invention contain
Piece is evident in efficacy to improving halitosis.
Test example 3：Present composition toxicity test
1st, the irritation test of complete to rat oral cavity and damaged mucous membrane
Experimental method：Rat 40 (male and female half and half) is taken, wherein 20 are made the damaged mucous membrane modeling in oral cavity：Wiped with coarse sandpaper
Oral mucosa, causes extensive and intensive blutpunkte occur；Another 20 are intact mucosal.Two class rats set respectively test medicine group and
Blank control group, every group 10 (male and female half and half).Lozenge group gives decoction (according to lozenge made from embodiment 6, by 50 tablets of lozenges
Fine powder is ground to form to be dissolved in 50ml water), blank control group gives same volume deionized water, and decoction is respectively dropped into rat oral cavity,
Every 0.2ml/ times, every 30min drop medicines, until decoction drop, complete continuous 7 days.Each mouse oral mucosa is observed during administration daily
Change；Animal was put to death in 24 hours after last medicine, take oral mucosa and make histological examination.
Experimental result：During administration, the oral mucosa of two intact mucosal group rats is showed no obvious abnormalities；And two broken
The oral mucosa of mucous membrane group rat is damaged in modeling early stage, visible damaged mucous membrane has different degrees of red, swollen, but without sepage, go out
Blood, the reaction such as fester, the 4th day red, swollen basic to disappear.Show that Traditional Chinese medicine lozenge of the present invention is complete to rat oral cavity and damaged mucous membrane is equal
Have no stimulation.
2nd, long term toxicity test
Experimental method：Body weight 140-165g Wistar systems regular grade rat 60 (male and female half and half) is taken, 2 are divided at random
Group, every group 30.Test group once gives lozenge 5, three times a day, successive administration 3 weeks.Control group is without any processing, protects
Demonstrate,prove two groups of mouse feeding environments identical.
Result of the test：Test group and the equal Non Apparent Abnormality of control group mice, test group have no toxic reaction, withdrawal observation 2
Week also has no obvious delay toxic reaction.Show that lozenge of the present invention is non-toxic.
Embodiment：
Embodiment 1：Treat the preparation of the Chinese medicine composition of halitosis
Formula：Radix pseudostellariae 87g, Chinese yam 61g, dried rhizome of rehmannia 20g, red sage root 38g, dark plum 59g, banksia rose 35g, wrinkled giant hyssop 19g, the root of Dahurain angelica
22g, grass-leaved sweetflag 8g, dried orange peel 10g
Preparation method：Take radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs
Decocted twice through water extraction, the water of total 10 times of medicinal material amount is added for the first time, decocted 2 hours, 200 mesh filtering reserved filtrate is standby, the
The secondary decocting for adding 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, is merged filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relatively
Density produces for 1.05-1.30 (60 DEG C) thick paste.
Embodiment 2：Treat the preparation of the Chinese medicine composition of halitosis
Formula：Radix pseudostellariae 98g, Chinese yam 70g, dried rhizome of rehmannia 28g, red sage root 47g, dark plum 70g, banksia rose 42g, wrinkled giant hyssop 26g, the root of Dahurain angelica
30g, grass-leaved sweetflag 12g, dried orange peel 15g
Preparation method：Take radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs
Decocted twice through water extraction, the water of total 10 times of medicinal material amount is added for the first time, decocted 2 hours, 200 mesh filtering reserved filtrate is standby, the
The secondary decocting for adding 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, is merged filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relatively
Density produces for 1.05-1.30 (60 DEG C) thick paste.
Embodiment 3：Treat the preparation of the Chinese medicine composition of halitosis
Formula：Radix pseudostellariae 101g, Chinese yam 76g, dried rhizome of rehmannia 33g, red sage root 51g, dark plum 74g, banksia rose 46g, wrinkled giant hyssop 28g, the root of Dahurain angelica
35g, grass-leaved sweetflag 14g, dried orange peel 17g
Preparation method：Take radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs
Decocted twice through water extraction, the water of total 10 times of medicinal material amount is added for the first time, decocted 2 hours, 200 mesh filtering reserved filtrate is standby, the
The secondary decocting for adding 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, is merged filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relatively
Density produces for 1.05-1.30 (60 DEG C) thick paste.
Embodiment 4：Treat the preparation of the Chinese medicine composition of halitosis
Formula：Radix pseudostellariae 110g, Chinese yam 81g, dried rhizome of rehmannia 37g, red sage root 54g, dark plum 77g, banksia rose 50g, wrinkled giant hyssop 30g, the root of Dahurain angelica
39g, grass-leaved sweetflag 16g, dried orange peel 19g
Preparation method：Take radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs
Decocted twice through water extraction, the water of total 10 times of medicinal material amount is added for the first time, decocted 2 hours, 200 mesh filtering reserved filtrate is standby, the
The secondary decocting for adding 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, is merged filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relatively
Density produces for 1.05-1.30 (60 DEG C) thick paste.
Embodiment 5：Treat the preparation of the Chinese medicine composition of halitosis
Formula：Radix pseudostellariae 119g, Chinese yam 94g, dried rhizome of rehmannia 46g, red sage root 62g, dark plum 88g, banksia rose 60g, wrinkled giant hyssop 35g, the root of Dahurain angelica
47g, grass-leaved sweetflag 19g, dried orange peel 23g
Preparation method：Take radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs
Decocted twice through water extraction, the water of total 10 times of medicinal material amount is added for the first time, decocted 2 hours, 200 mesh filtering reserved filtrate is standby, the
The secondary decocting for adding 8 times of amounts is boiled 1 hour, the filtering of 200 mesh, is merged filtrate twice, is taken said extracted liquid to be concentrated under reduced pressure into relatively
Density produces for 1.05-1.30 (60 DEG C) thick paste.
Embodiment 6：It is prepared by the lozenge for treating halitosis
Formula：Radix pseudostellariae 101g, Chinese yam 76g, dried rhizome of rehmannia 33g, red sage root 51g, dark plum 74g, banksia rose 46g, wrinkled giant hyssop 28g, the root of Dahurain angelica
35g, grass-leaved sweetflag 14g, dried orange peel 17g
Preparation method：(1) radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, dried orange peel Chinese medicine drink are taken
Piece is decocted twice through water extraction, and the water of total 10 times of medicinal material amount is added for the first time, is decocted 2 hours, and 200 mesh filtering reserved filtrate is standby,
The decoctings of second of addition, 8 times of amounts are boiled 1 hour, and the filtering of 200 mesh merges filtrate twice, takes said extracted liquid to be concentrated under reduced pressure into phase
It is standby to the thick paste that density is 1.05-1.30 (60 DEG C)；
(2) reduced vacuum is dried under the conditions of taking thick paste, 50 DEG C, and dry cream crushed 100 mesh sieves；Take 45g PVP K30s,
It is well mixed, granulation, after 50 DEG C of dryings, whole grain adds 20g magnesium stearates, is well mixed, tabletting is obtained after 325g mannitol
Buccal tablet.
Claims (9)
1. a kind of Chinese medicine composition for treating halitosis, by weight, it is characterised in that：By 87-119 parts of radix pseudostellariae, Chinese yam 61-
94 parts, 20-46 parts of the dried rhizome of rehmannia, 38-62 parts of the red sage root, 59-88 parts of dark plum, 35-60 parts of the banksia rose, 19-35 parts of wrinkled giant hyssop, 22-47 parts of the root of Dahurain angelica,
8-19 parts of grass-leaved sweetflag, 10-23 parts of dried orange peel are made.
2. Chinese medicine composition according to claim 1, by weight, it is characterised in that：By 98-110 parts of radix pseudostellariae, mountain
70-81 parts of medicine, 28-37 parts of the dried rhizome of rehmannia, 47-54 parts of the red sage root, 70-77 parts of dark plum, 42-50 parts of the banksia rose, 26-30 parts of wrinkled giant hyssop, root of Dahurain angelica 30-
39 parts, 12-16 parts of grass-leaved sweetflag, 15-19 parts of dried orange peel be made.
3. Chinese medicine composition according to claim 1, by weight, it is characterised in that：By 101 parts of radix pseudostellariae, Chinese yam
76 parts, 33 parts of the dried rhizome of rehmannia, 51 parts of the red sage root, 74 parts of dark plum, 46 parts of the banksia rose, 28 parts of wrinkled giant hyssop, 35 parts of the root of Dahurain angelica, 14 parts of grass-leaved sweetflag, dried orange peel 17
Part is made.
4. according to any described Chinese medicine compositions of claim 1-3, it is characterised in that described composition can directly be ground
Mixed into powder or the active component extracted by this area conventional extraction techniques and pharmaceutically acceptable pharmaceutic adjuvant system
Into various pharmaceutical dosage forms.
5. according to the excipient substance described in claim 4, it is characterised in that described excipient substance can for sweetener, acid,
Preservative, wetting agent, lubricant, wetting agent, disintegrant, diluent and adhesive.
6. a kind of preparation method for the Chinese medicine composition for treating halitosis, it is characterised in that：Comprise the following steps：
Radix pseudostellariae, Chinese yam, the dried rhizome of rehmannia, the red sage root, dark plum, the banksia rose, wrinkled giant hyssop, the root of Dahurain angelica, grass-leaved sweetflag, the dried orange peel prepared slices of Chinese crude drugs are taken to be decocted through water extraction
Boil twice, the water of total 10 times of medicinal material amount is added for the first time, decoct 2 hours, 200 mesh filtering reserved filtrate is standby, second of 8 times of addition
The decocting of amount is boiled 1 hour, the filtering of 200 mesh, merges filtrate twice, takes said extracted liquid to be concentrated under reduced pressure into relative density for 1.05-
The thick paste of 1.30 (60 DEG C)；Various pharmaceutical dosage forms are made with pharmaceutically acceptable pharmaceutic adjuvant in thick paste again.
7. pharmaceutical dosage form according to claim 6, it is characterised in that：Described pharmaceutical dosage form is buccal tablet, spray, bag
Make tea.
8. a kind of preparation method for the buccal tablet for treating halitosis, it is characterised in that：Comprise the following steps：
Reduced vacuum is dried under the conditions of taking thick paste, 40-60 DEG C, and dry cream crushed 100 mesh sieves；Take 35-55 parts of PVP K30s,
It is well mixed after 300-350 portions of mannitol, granulation, after 40-60 DEG C of drying, whole grain adds 14-26 parts of magnesium stearates, mixing
Uniformly, tabletting, obtains buccal tablet.
9. the preparation method of the buccal tablet for the treatment of halitosis according to claim 8, it is characterised in that：Comprise the following steps：
Reduced vacuum is dried under the conditions of taking thick paste, 50 DEG C, and dry cream crushed 100 mesh sieves；Take 45 parts of PVP K30s, 325 parts of sweet dews
It is well mixed, granulation, after 50 DEG C of dryings, whole grain adds 20 parts of magnesium stearates, is well mixed, tabletting obtains buccal tablet after alcohol.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102166315A (en) * | 2011-04-15 | 2011-08-31 | 北京身心康生物科技有限公司 | Traditional Chinese medicine preparation for people with damp heat constitution to remove and resolve humidity, preparation method thereof and application thereof |
| CN103638387A (en) * | 2013-12-16 | 2014-03-19 | 王纯治 | Chinese medicine preparation for treating ozostomia and preparation method thereof |
| CN105250793A (en) * | 2015-11-23 | 2016-01-20 | 俞成莲 | Medicine used for treating halitosis |
| CN106692753A (en) * | 2016-12-31 | 2017-05-24 | 湖南灼华生物科技有限公司 | Traditional Chinese medicine composition for improving halitosis, and preparation method and application thereof |
-
2017
- 2017-06-12 CN CN201710439575.7A patent/CN107281360A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102166315A (en) * | 2011-04-15 | 2011-08-31 | 北京身心康生物科技有限公司 | Traditional Chinese medicine preparation for people with damp heat constitution to remove and resolve humidity, preparation method thereof and application thereof |
| CN103638387A (en) * | 2013-12-16 | 2014-03-19 | 王纯治 | Chinese medicine preparation for treating ozostomia and preparation method thereof |
| CN105250793A (en) * | 2015-11-23 | 2016-01-20 | 俞成莲 | Medicine used for treating halitosis |
| CN106692753A (en) * | 2016-12-31 | 2017-05-24 | 湖南灼华生物科技有限公司 | Traditional Chinese medicine composition for improving halitosis, and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| 崔淑华: "运脾汤治疗口臭52例临床观察", 《河北中医》 * |
| 陈文贵: "治疗口臭验方", 《家庭中医药》 * |
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