CN100998577A - Triclosan compounding lotion for external use and its preparing method - Google Patents

Abstract

An exterior-applied lotion or gel of triclosan for preventing and treating the infectious gynecologic inflammation is proportionally prepared from triclosan, pronopol, gel matrix and other additives including surfactant. Its preparing process is also disclosed.

Description

A kind of triclosan compounding lotion for external use and preparation method thereof

Technical field

The invention belongs to the medical composition field, be specifically related to a kind of triclosan compounding washing liquid that is used for gynecological inflammation and gel and preparation method thereof, the inflammation that this gel is used for the treatment of or prevents gynecological infection to cause.

Background technology

Vulvitis and vaginitis are numerous women's commonly encountered diseases and frequently-occurring diseases, and according to data report in one's early years, about 80% women suffers from pudendum disease in various degree.Particularly unclean sexual intercourse; Male's sexual intercourse of women and trouble morbidity according to reports, the single infection rate reaches 80-90%; Male and the female sexual intercourse of suffering from morbidity have 20-50% infected.The back symptom is lighter though the women infects, and complication is more than the male, can cause cervicitis, endometritis, defeated Guan Yan, pelvic inflammatory disease, infertile etc.

Along with social change, the men and women is in system's infectious disease and increases year by year, is seriously perplexing people's life and cause, and family and harmonious doings.Raising along with people's living standard, the enhancing of health perception, the daily cleaning health of men and women's property pudendum, women's menstrual period, puerperal, and provide sanitation and hygiene, prophylactic health care product or medicine to become people's daily demand before and after men and women's sexual life.

Be used for pudendum, have the health care product (" dissipation medicament ") of antibacterial action, come across market in China with commodity and start from the eighties late period in last century, influential in the whole nation is " JIEERYIN " and " 102 health dew ".Subsequently, this type of commodity fast development, even to this day, it is various in style.The dosage form of in the market " washing liquid ", summary can be categorized as: the concentrated type washing liquid; The spary coating type washing liquid; Shampoo type washing liquid.

The concentrated type washing liquid: medicinal liquid concentrates, time spent dilute with water 20-50 doubly after, as traditional washing methods, demibain or bathing.Cleaning, decontamination, antibacterial effect are better; But it is very not convenient to use, and the time spent needs dilution, and large usage quantity, and general demibain needs diluent more than 1500ML, and one bottle " washing liquid " is several times have more than is needed.General concentrated type washing liquid manufacturing cost is higher relatively, and Macrodilution liquid just goes with the back, causes into the wasting of resources, has increased the financial burden of consumer accordingly.

Spary coating type washing liquid: be that the medicinal liquid of activity is sprayed at external genital with the method for spraying.Though it is convenient to use, after the general spraying not water remove, thus, the secretions of pudendum, dirt can not go out clearly, residues in pudendum, it is poor therefore to clean clean effect.This type of " washing liquid " because of packing (aerosol apparatus) cost height, the financial burden of consumer is also big.

Shampoo type washing liquid: this type of " washing liquid " be similar shampoo (essence is exactly that shampoo adds antibacterial) on dosage form, removes the surfactant of drugs with function external demand with high concentration, could form dosage form.Easy to use, each consumption is few, and cleaning, clean effect are good; But degreasing power is too strong, with afterwards genital skin is dry and astringent, cutin is facilitated, squama increases; Pubes are uninteresting, easily broken; Mucosa stimulates or damaged mucosa is caused shallow table capillary rupture and hemorrhage easily and cause because face table tension force significantly reduces; During washing, the pudendum foam is too abundant, also inconvenience is cleaned.

Washing liquid or spray that clean cloudy product on the Chinese market is mostly made for Chinese medicine extract, clean etc. as JIEERYIN, FUYINJIE, skin, but the antibacterial action of Chinese medicine is limited, it is the washing liquid that chemical products or medicine are made that part is also arranged, the antibacterial activity composition is based on hibitane, chlorhexidine acetate, bromo geramine (benzalkonium bromide), PVP-iodine, metronidazole etc., its antibacterial action is not strong, and side effect is big.

In the face of living standard improves, hygienic habit is improved, and to the high more women colony of clean cloudy skin protection demand, the exploitation antibacterial action is strong, and few side effects, pudendum care product easy to use are very necessary, and bigger market value is arranged.For this reason, the inventor has invented the compound recipe pudendum washing liquid that contains triclosan (Triclosan) and Bronopol (Bronopol) through years of researches and test, especially its gel, this gel antibacterial action is strong, does not need demibain, adhesiveness strong, but easy cleaning, untoward reaction such as nonirritant.

Triclosan (chemical name: 2,4,4 '-three chloro-2 '-dihydroxy diphenyl ether) for general common antibacterial, fungus, and pathogen such as yeast, all have the effect of killing and inhibitory action, multiple fungus and virus are all had efficient inhibitory or killing effect, and effect is rapid and lasting.The endochylema film that the antimicrobial main site of action of triclosan is an antibacterial, stop antibacterial to necessary amino acid whose picked-up during Mlc, then can make antibacterial endochylema film destroy during bacteriocidal concentration, cellular content is excessive, and is all effectively same to non-Resistant strain and Resistant strain.Therefore, triclosan is widely used in efficient medicated soap, health fancy soap, sanitary lotion, removes bromhidrosis, foot aerosol etc. in life.More highly purified triclosan (Bock bacterium ether) is widely used in the curative effect toothpaste and collutory of treatment gingivitis, periodontitis and oral ulcer etc.Triclosan is added in collutory or the toothpaste, and the oral cavity pathogen is had very strong killing action, reduces gingival infection and eliminates halitosis; Add among the fragrant Suds of efficient medicine Suds, Wei Sheng, have the function of sterilizing and inhibition body odor; Add in the shampoo, but relieving itching and removing dandruff; Add in bath shampoo and the handwashing liquid, but disinfecting and decontaminating; Add in the dish washing detergent, can eliminate antibacterial and abnormal flavour on the tableware; Add in cleansing milk, the cleansing cream, can kill the pathogen that causes acne; Add in the dusting powder for infants, can prevent the generation of miliaria and erythra; Add in the aerosol, be used for air purifying and sterilizing, the effective flu-prevention of level etc. are by the respiratory tract disease of aerial infection; Also be used for disinfected paper napkin, antibiotic textile fabric, antibiotic plastic etc.; More highly purified Bock bacterium ether is used for pharmaceutical preparation, the generation of treatment seborrheic dermatitis, folliculitis, rosacea, eczema, herpes, contact dermatitis, angular cheilitis, acne etc. and infection prevention disease (as sexually transmitted disease (STD), digestive tract, respiratory tract disease); Also be used for surgical medical equipment, sterilization wound etc.

Chinese patent CN1480221 discloses a kind of disposable disinfecting gel that contains triclosan in 2004, can be used for sterilization, the sterilization, antibacterial of skin and body surface, the generation of prevention contact infectious disease (for example SARS, hepatitis A, hepatitis B virus, HIV (human immunodeficiency virus) HIV etc.).

Bronopol has broad spectrum antibiotic activity, can effectively suppress gram negative bacteria, positive bacteria, yeast and mycete, is applicable to the cream frost, reveals resident type and rinse-off products such as liquid, shampoo, hair conditioner, wet tissue.At present, this product all is extensive use of in the U.S., Britain and Germany etc.

Chinese patent CN1101550 (nineteen ninety-five) discloses a kind of Chinese medicine compound external wash liquid that contains Bronopol, is used for male and female pudendum and skin, particularly is exclusively used in the external wash liquid of gynaecopathia.

The inventor is unexpected under study for action to find that triclosan and Bronopol are combined into compound recipe pudendum washing liquid, and its degerming antiinflammatory effect obviously is better than single washing liquid of using of triclosan or Bronopol, also be better than new clean you go out, pudendum lotion such as hibitane, make gel, not only easily wash, nonirritant, and because of the adhesiveness of gel, active component is fully contacted with skin, raising is shortened treatment time, in addition to the killing action of antibacterial, because of not needing demibain, the convenient use.

Summary of the invention

The invention provides a kind of triclosan compounding lotion for external use, contain triclosan (Triclosan), Bronopol (Bronopol), wherein the weight of triclosan and Bronopol is 1: 1-5: 1.This washing liquid can be used for the prevention and the treatment of women's pudendum inflammation caused by bacterial infection, the cleaning and disinfection that also can be used for male and female pudendum, prevent that the sexually transmitted disease (STD) that sexual intercourse causes infects, its effect is better than the effect of single usefulness of effective active components, also be better than new clean you go out, pudendum lotion such as hibitane.This compound recipe washing liquid has obvious synergistic effect.

Above-mentioned triclosan compounding pudendum washing liquid also comprises thickening agent or gel and water.

The present invention also provides a kind of triclosan compounding gel, it is characterized in that: comprise the triclosan that percentage by weight is 0.01-0.5%, the Bronopol of 0.01-0.1%, the gel-type vehicle of 0.1-1%.

Above-mentioned said gel-type vehicle is the polyacrylic acid resin, preferred carbomer (carbomer).

Triclosan compounding pudendum washing liquid of the present invention or gel also comprise and are selected from one or more following adjuvants: emulsifying agent, PH adjustment, electrolyte, stabilizing agent, water; Said emulsifying agent is polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine or their mixture; The PH regulator is a triethanolamine, and consumption is 0-5%; Stabilizing agent is a disodiumedetate, and electric angle matter is sodium chloride.

Triclosan compounding gel of the present invention also can further comprise Oleum menthae, and the consumption of Oleum menthae is 0.01-0.5% (weight), by weight percentage.

Preferred prescription:

The triclosan preferred weight ratio is 0.1-0.2%, more preferably 0.15%, and the commodity of pure triclosan are called " Bock bacterium ether ", preferred Bock bacterium ether; The Bronopol preferred weight ratio is 0.05%; The polyacrylic acid resin is as carbomer (carbomer940,941 or 934), weight ratio preferred 0.5%; The weight ratio of polyoxyethylene lauryl ether sodium sulfate is 1-8%, preferred 4%, and the weight ratio of cocamidopropyl propyl amide dimethyl betaine is 1-8%, preferred 4%; The weight ratio of disodiumedetate is 0.01-0.1%, preferred 0.05%; The triethanolamine weight ratio is 0.1-5%, preferred 1%; The weight ratio of Oleum menthae is preferably 0.1%, and weight sodium chloride is than for 0.1-1%, and is preferred 0.5%, and all the other be water, preferably deionized water.

The present invention also provides a kind of method for preparing the triclosan compounding gel, comprises following process:

A. it is soluble in water to take by weighing triclosan, emulsifying agent, electrolyte, and heating is stirred, and makes solution;

B. take by weighing gel-type vehicle, stabilizing agent is soluble in water, high speed shear stirs, and makes colloidal sol;

C. the colloidal sol that obtains of solution that step a is obtained and step b mixes, and adds Bronopol, Oleum menthae and Ph regulator again and stirs, and makes the gel of homogeneous, and bottling promptly.

Triclosan compounding gel of the present invention is used for prevention and treats the bacterial infection that causes and the vaginitis of women woman's pudendum (pudendum) a variety of causes, also can be used for male genitals sterilizing and cleaning, prevents the contact bacterial infection.

Triclosan compounding washing liquid of the present invention or gel, its sterilization and bacteriostasis all are better than triclosan or Bronopol list washing liquid, have obvious sterilization and antibacterial potentiation, especially make gel, not only improved therapeutic effect, but also have nonirritant, untoward reaction is few, the characteristics of easy cleaning, improved patient's compliance, do not needed demibain, used more more convenient than demibain.Triclosan compounding washing liquid of the present invention or gel promptly can be used as disinfectant, but also medicine.Pour out during use in right amount on hand, place pudendum to crumple then to foam, leave standstill 1-3 minute after, the water flushing gets final product.

Specific embodiment

Following examples are used to further specify the present invention, but do not limit the scope of the invention.

Embodiment 1 gel

Prescription (weight ratio):

Triclosan 0.15%,

Bronopol 0.05%

Carbomer (940,941 or 934) 0.5%;

Polyoxyethylene lauryl ether sodium sulfate 4%,

Cocamidopropyl propyl amide dimethyl betaine 4%;

Disodiumedetate 0.05%;

Triethanolamine 1%;

Oleum menthae 0.1%,

Sodium chloride 0.5%,

All the other are added to 100% for deionized water

Preparation technology: take by weighing triclosan, polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine and sodium chloride in the prescription ratio and mix, add deionized water dissolving, heating is stirred, and makes solution; Carbomer and disodiumedetate that other takes by weighing weight ratio place remaining deionized water, and high speed shear stirs, and makes colloidal sol; Above-mentioned solution and colloidal sol are mixed, add triethanolamine, Bronopol and the Oleum menthae of weight ratio again, mixed, be stirred to even, transparent gel-form, bottling is promptly then.

The gel that this enforcement makes is killed fast or is suppressed escherichia coli, staphylococcus aureus, Candida albicans, and antibacterial effective percentage is 100%.

Embodiment 2 gels

Prescription (weight ratio):

Triclosan 0.02%

Bronopol 0.1%

Carbomer (940,941 or 934) 0.8%

Polyoxyethylene lauryl ether sodium sulfate 6%

Cocamidopropyl propyl amide dimethyl betaine 2%

Disodiumedetate 0.05%

Triethanolamine 1%

Oleum menthae 0.1%

Sodium chloride 0.5%

All the other add to 100% for deionized water

Preparation technology: take by weighing triclosan, polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine and sodium chloride in the prescription ratio and mix, add deionized water dissolving, heating is stirred, and makes solution; Carbomer and disodiumedetate that other takes by weighing weight ratio place remaining deionized water, and high speed shear stirs, and makes colloidal sol; Above-mentioned solution and colloidal sol are mixed, add triethanolamine, Bronopol and the Oleum menthae of weight ratio again, mixed, be stirred to even, transparent gel-form, bottling is promptly then.

Embodiment 3 gels

Prescription (weight ratio):

Triclosan 0.2%,

Bronopol 0.01%

Carbomer (940,941 or 934) 0.2%;

Polyoxyethylene lauryl ether sodium sulfate 4%,

Cocamidopropyl propyl amide dimethyl betaine 4%;

Disodiumedetate 0.05%;

Triethanolamine 1%;

Sodium chloride 0.5%,

All the other add to 100% for deionized water

Preparation technology: take by weighing triclosan, polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine and sodium chloride in the prescription ratio and mix, add deionized water dissolving, heating is stirred, and makes solution; Carbomer and disodiumedetate that other takes by weighing weight ratio place remaining deionized water, and high speed shear stirs, and makes colloidal sol; Above-mentioned solution and colloidal sol are mixed, add triethanolamine, Bronopol and the Oleum menthae of weight ratio again, mixed, be stirred to even, transparent gel-form, bottling is promptly then.

Embodiment 4 washing liquids

Prescription

Triclosan 0.15%

Bronopol 0.5%

Acritamer 940 0.1%

Polyoxyethylene lauryl ether sodium sulfate 6%

Disodiumedetate 0.05%

Triethanolamine 1%

Sodium chloride 0.5%

All the other add to 100% for deionized water

Preparation technology: take by weighing triclosan, polyoxyethylene lauryl ether sodium sulfate and sodium chloride in the prescription ratio and mix, add deionized water dissolving, heating is stirred, and makes solution; Acritamer 940 and disodiumedetate that other takes by weighing weight ratio place remaining deionized water, and high speed shear stirs, and makes solution; Above-mentioned two kinds of solution are mixed, add the triethanolamine and the Bronopol of weight ratio again, mixed, be stirred to even, transparence liquid, bottling is promptly then.

The comparative example

Prescription (weight ratio):

Triclosan 0.15%,

Carbomer (940,941 or 934) 0.5%;

Polyoxyethylene lauryl ether sodium sulfate 4%,

Cocamidopropyl propyl amide dimethyl betaine 4%;

Disodiumedetate 0.05%;

Triethanolamine 1%;

Oleum menthae 0.1%,

Sodium chloride 0.5%,

All the other add to 100% for deionized water

Preparation technology: take by weighing triclosan, polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine and sodium chloride in the prescription ratio and mix, add deionized water dissolving, heating is stirred, and makes solution; Carbomer and disodiumedetate that other takes by weighing weight ratio place remaining deionized water, and high speed shear stirs, and makes colloidal sol; Above-mentioned solution and colloidal sol are mixed, add the triethanolamine and the Oleum menthae of weight ratio again, mixed, be stirred to even, transparent gel-form, bottling is promptly then.

Bactericidal assay

The gel that embodiment 1 and comparative example the are obtained contrast test that sterilizes, the former claims " test sample group ", the latter is called " positive reference substance group ", undertaken by " the disinfection technology standard first fascicle experimental technique standard ", 2,5,10,20min " test sample group " and " positive reference substance group " by the dilution of 1: 1 water, the bactericidal action time:.Experimental strain: staphylococcus aureus ATCC6538 (the 3rd generation), escherichia coli 8099 (the 4th generation), Candida albicans ATCC10231 (the 4th generation).The result proves that the test sample group obviously is better than the positive reference substance group to staphylococcus aureus, escherichia coli, Candida albicans killing effect, sees the following form 1 and table 2.

The gel of table 1 embodiment 1 (test sample) is to the bactericidal action of test organisms

Test organisms	Concentration	Matched group bacterium number	The sterilizing rate (%) of effect different time (min)
							Test sample: water	(cfu/ml)	2	5	10	20
	The staphylococcus aureus e coli Candida albicans	1∶1 1∶1 1∶1	2.98×10 5 2.63×10 5 4.89×10 5	100 98.17 99.90	100 99.92 99.97	100 99.95 100							100 99.95 100

Table 2 comparative example's gel (positive reference substance) is to the bactericidal action of test organisms

Test organisms	Concentration	Matched group bacterium number	Make the sterilizing rate (%) of firm different time (min)
							Positive reference substance: water	(cfu/ml)	2	5	10	20
	The staphylococcus aureus e coli Candida albicans	1∶1 1∶1 1∶1	2.98×10 52.63×10 54.89×10 5	100 85.17 82.93	100 86.91 87.97	100 89.91 90.00							100 89.90 92.10

Skin irritation test

There is not skin irritation through the zoopery evidence.

Test is undertaken by " disinfection technology standard " (2002 editions) skin irritation test regulation, to be tried thing (gel of embodiment 1) 0.5ml and evenly be smeared rabbit unhairing district, opposite side is the blank unhairing, district's sealing 4 hours, smeared continuously 14 days, after smearing for the last time, sealed 4 hours, remove with warm water then and tried behind the thing to observe respectively in 1,24,48 hour dermoreaction, the integral mean value of different time observation as a result all is 0, see Table 3, the explanation of record experimental result: gel of the present invention is to the skin nonirritant.

Table 3 rabbit intact skin irritation test

Number of animals	Sex	Body weight (Kg)	Skin irritation reaction scoring
															1 hour				24 hours				48 hours
			Erythema		Edema		Erythema		Edema		Erythema		Edema
															Sample	Right	Sample	Right	Sample	Right	Sample	Right	Sample	Right	Sample	Right
			1 2 3 4	Robust	2.60 2.72 2.85 2.90	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0	0 0 0 0													0 0 0 0	0 0 0 0	0 0 0 0
The total mark average															0				0				0
			The stimulus intensity classification			Nonirritant				Nonirritant				Nonirritant

Antibacterial activity contrast test with bromo geramine, hibitane

The antibacterial activity of the washing liquid (being called sample sets) of embodiment 4 and bromo geramine, hibitane is carried out external contrast test, result such as following table 4.

The antibacterial activity contrast test of the washing liquid of table 4 embodiment 4 and bromo geramine, hibitane

Trial target bromo geramine hibitane group sample sets	Antibacterial		Fungus+-++	Virus++ ++
					G+ + ++ ++	G- - ++ ++

Annotate, " ++ " be that killing effect is best, "+" is that killing effect is general, "-" kills for difficulty

The explanation of above result of the test: antibacterium, fungus and the virus function of compound recipe washing liquid of the present invention or gel are better than bromo geramine, hibitane, especially antifungal and viral aspect better effects if.

Claims (10)

1, a kind of triclosan compounding lotion for external use comprises triclosan and Bronopol, and wherein, the weight ratio of triclosan and Bronopol is 1: 1-5: 1.

2, the described triclosan compounding lotion for external use of claim 1 also comprises thickening agent or gel-type vehicle and water.

3, a kind of triclosan compounding gel that is used for gynecological inflammation comprises the triclosan that percentage by weight is 0.01-0.5%, the Bronopol of 0.01-0.1%, the gel-type vehicle of 0.1-1%.

4, triclosan compounding gel as claimed in claim 3, its said gel-type vehicle is the polyacrylic acid resin.

5, triclosan compounding gel as claimed in claim 4, said polyacrylic acid resin is a carbomer.

6, triclosan compounding gel as claimed in claim 3 also comprises being selected from one or more following adjuvants: emulsifying agent, PH adjustment, electrolyte, stabilizing agent, water.

7, triclosan compounding gel as claimed in claim 6, said emulsifying agent are polyoxyethylene lauryl ether sodium sulfate, cocamidopropyl propyl amide dimethyl betaine or their mixture; The PH regulator is a triethanolamine, and consumption is 0-5%; Stabilizing agent is a disodiumedetate.

8, triclosan compounding gel as claimed in claim 2 also further comprises Oleum menthae.

9, triclosan compounding gel as claimed in claim 8, the consumption of said Oleum menthae is 0.01-0.5%, by weight percentage.

10, a kind of method for preparing the triclosan compounding gel comprises following process:

A. it is soluble in water to take by weighing triclosan, emulsifying agent and electrolyte, and heating is stirred, and makes solution;

B. take by weighing gel-type vehicle, stabilizing agent is soluble in water, high-speed stirred is made colloidal sol;

C. the colloidal sol that obtains of solution that step a is obtained and step b mixes, and adds Bronopol, Oleum menthae and Ph regulator again, stirs, and makes the gel of homogeneous, and bottling promptly.