CN112316017A

CN112316017A - Gynecological antibacterial gel and preparation method thereof

Info

Publication number: CN112316017A
Application number: CN202011303433.6A
Authority: CN
Inventors: 杨理文
Original assignee: Shanxi Kangle Industry Co ltd
Current assignee: Shanxi Kangle Industry Co ltd
Priority date: 2020-11-19
Filing date: 2020-11-19
Publication date: 2021-02-05

Abstract

The application relates to the field of antibacterial gel, and particularly discloses gynecological antibacterial gel and a preparation method thereof; the gynecological bacteriostatic gel comprises the following raw materials in parts by weight: 80-90 parts of radix sophorae flavescentis, 70-80 parts of golden cypress, 80-90 parts of fructus cnidii, 50-60 parts of gallnut, 40-50 parts of safflower, 1-2 parts of oviductus ranae, 1-2 parts of vegetable essential oil, 8-10 parts of glycerol, 10-15 parts of triethanolamine, 10-15 parts of carbomer, 2-3 parts of ethylparaben, 1-2 parts of benzalkonium bromide and the balance of water, and the balance is water and is added to the total amount of 1000 parts. The gynecological bacteriostatic gel has a good bacteriostatic effect and has no irritation effect on vaginal mucosa.

Description

Gynecological antibacterial gel and preparation method thereof

Technical Field

The application relates to the field of bacteriostatic gels, in particular to a gynecological bacteriostatic gel and a preparation method thereof.

Background

Gynecological inflammation such as vaginitis, cervical erosion, etc. is a common disease and frequently encountered disease of women. One of the major current treatments for these gynecological inflammations is drug therapy. The common drug therapy comprises oral drugs and external therapy, and the external therapy mainly comprises suppository, effervescent agent administration treatment and traditional Chinese medicine fumigation and washing. Although the external therapy has a certain treatment effect, the use effect of patients is not ideal, for example, most of the medicines for treating cervical erosion are suppositories, the release of the medicine effect of the suppositories is slow, and the medicines are dissolved to form liquid which flows out of the vagina; effervescent agents can cause drying of the skin tissue surface, causing discomfort; the traditional Chinese medicine is inconvenient to use by fumigation.

Mucosal administration refers to the administration of a drug in intimate contact with the surface of a biological mucosa and into the circulatory system via epithelial cells. Mucosal administration has advantages such as avoidance of first-pass effect, balanced blood concentration, long action time, and small dosage and high bioavailability because of abundant submucosal capillaries. Chinese medicinal gel is a method for treating gynecological inflammation by mucosa administration which is emerging in recent years.

In view of the above-mentioned related technologies, the inventor considers that the existing traditional Chinese medicine gel has no obvious bacteriostatic effect, and needs to provide a gynecological bacteriostatic gel and a preparation method thereof.

Disclosure of Invention

In order to improve the bacteriostatic effect of the traditional Chinese medicine gel, the application provides a gynecological bacteriostatic gel and a preparation method thereof.

In a first aspect, the application provides a gynecological bacteriostatic gel, which adopts the following technical scheme:

the gynecological bacteriostatic gel comprises the following raw materials in parts by weight:

80-90 parts of radix sophorae flavescentis, 70-80 parts of golden cypress, 80-90 parts of fructus cnidii, 50-60 parts of gallnut, 40-50 parts of safflower, 1-2 parts of oviductus ranae, 1-2 parts of vegetable essential oil, 8-10 parts of glycerol, 10-15 parts of triethanolamine, 10-15 parts of carbomer, 2-3 parts of ethylparaben, 1-2 parts of benzalkonium bromide and the balance of water, and the balance is water and is added to the total amount of 1000 parts.

By adopting the technical scheme, the gynecological inflammation is usually caused by maladjustment of microbial flora in the vagina, and most of harmful bacteria in the vagina are staphylococcus aureus, escherichia coli and candida albicans. Radix Sophorae Flavescentis contains various alkaloids and flavonoids, and has effects of clearing heat and eliminating dampness; cortex Phellodendri contains berberine, and has effects of clearing heat, eliminating dampness, clearing pathogenic fire, and removing toxic substance; fructus Cnidii contains coumarin components, and has effects of dispelling pathogenic wind, removing dampness, killing parasites and relieving itching; galla chinensis contains tannic acid, and has effects of lowering fire and removing toxic substance; carthami flos contains flavone and volatile oil, and has effects of promoting blood circulation, dredging channels, removing blood stasis, and relieving pain. Because the five traditional Chinese medicines of the lightyellow sophora root, the golden cypress, the common cnidium fruit, the Chinese gall and the safflower are compatible, the five traditional Chinese medicines jointly play a role in inhibiting the growth of staphylococcus aureus, escherichia coli and candida albicans, and the oviductus ranae with the effects of preventing senility, nourishing yin and beautifying is supplemented, the gynecological bacteriostatic gel has a good bacteriostatic effect.

Optionally, the plant essential oil is rose essential oil.

By adopting the technical scheme, the rose essential oil not only has a nourishing effect, but also has an antibacterial effect on staphylococcus aureus, so that the antibacterial effect of the gynecological antibacterial gel is further improved.

Optionally, the gynecological antibacterial gel further comprises 0.5-1.5 parts by weight of nano-silver and 1-3 parts by weight of hypericum perforatum extract.

By adopting the technical scheme, the nano-silver and the hypericum perforatum have good bacteriostatic effects on staphylococcus aureus, escherichia coli and candida albicans, and the bacteriostatic effect of the gynecological bacteriostatic gel can be further improved by adding the nano-silver and the hypericum perforatum.

Optionally, the particle size of the nano silver is 20-50 nm.

By adopting the technical scheme, the particle size of the nano-silver is related to the bacteriostatic effect of the nano-silver, and the bacteriostatic effect of the gynecological bacteriostatic gel can be further improved by controlling the particle size of the nano-silver.

Optionally, the preparation method of the hypericum perforatum extract comprises the following steps: pulverizing herba Hyperici perforati, sieving to obtain coarse powder, adding 6-8 times of 80-85% ethanol solution, ultrasonic extracting for 1-2 hr, filtering, recovering ethanol from filtrate, and concentrating under reduced pressure to obtain extract with relative density of 1.10-1.20(60 deg.C), i.e. herba Hyperici perforati extract.

By adopting the technical scheme, the hypericum perforatum is ultrasonically extracted by ethanol, which is beneficial to the dissolution of antibacterial active ingredients such as hyperforin and aromatic oil ingredients, thereby further improving the antibacterial effect of the gynecological antibacterial gel.

Optionally, the weight ratio of the nano silver to the hypericum perforatum is 1: 2.

by adopting the technical scheme, the proportion of the nano-silver and the hypericum perforatum is controlled within a proper range, and the nano-silver and the hypericum perforatum are synergistic, so that the bacteriostatic effect of the gynecological bacteriostatic gel can be further improved.

In a second aspect, the application provides a preparation method of gynecological bacteriostatic gel, which adopts the following technical scheme:

a preparation method of gynecological bacteriostatic gel comprises the following steps:

s1: selecting radix Sophorae Flavescentis, cortex Phellodendri, fructus Cnidii, Galla chinensis, Carthami flos, and oviductus Ranae, cleaning;

dissolving ethylparaben in appropriate amount of ethanol to obtain ethylparaben solution for use;

soaking carbomer in appropriate amount of water for 24 hr to swell completely to obtain carbomer gel matrix;

s2: decocting radix Sophorae Flavescentis, cortex Phellodendri, fructus Cnidii, Galla chinensis and Carthami flos in water twice, mixing filtrates, concentrating to obtain extract with relative density of 1.10-1.20(60 deg.C), precipitating with ethanol, collecting supernatant, and recovering ethanol until no ethanol smell exists to obtain Chinese medicinal extract;

s3: adding ethylparaben solution and Chinese medicinal extract into carbomer gel matrix, adding other raw materials, stirring, adding water to desired volume, adding triethanolamine to adjust pH to 6-7, mixing, and packaging.

By adopting the technical scheme, the bacteriostatic gel prepared by the method has a good bacteriostatic effect.

Optionally, the specific conditions of decocting twice with water in S2 are as follows: adding 8-10 times of water for the first time, decocting for 1.5-2.5 hr, adding 6-8 times of water for the second time, decocting for 1-2 hr, and filtering.

By adopting the technical scheme, the decoction conditions are controlled, so that the dissolution of the bacteriostatic active ingredients in the traditional Chinese medicine is facilitated, and the bacteriostatic effect of the gynecological bacteriostatic gel is further improved.

In summary, the present application has the following beneficial effects:

1. the gynecological bacteriostatic gel has the beneficial effects that the five traditional Chinese medicines of the lightyellow sophora root, the golden cypress, the common cnidium fruit, the Chinese gall and the safflower are compatible, so that the five traditional Chinese medicines jointly play a role in inhibiting the growth of staphylococcus aureus, escherichia coli and candida albicans, and the oviductus ranae with the effects of preventing aging, nourishing yin and beautifying is supplemented, so that the gynecological bacteriostatic gel has a good bacteriostatic effect.

2. The application preferably adopts nano-silver and the hypericum perforatum extract, the nano-silver and the hypericum perforatum extract have an inhibiting effect on staphylococcus aureus, escherichia coli and candida albicans, and the nano-silver and the hypericum perforatum extract have a synergistic effect when being compounded, so that the bacteriostatic effect of the gynecological bacteriostatic gel can be further improved.

Detailed Description

The present application will be described in further detail with reference to examples.

Staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 11229) and Candida albicans (ATCC 10231) were purchased from China center for culture Collection; tryptone, yeast extract, sodium chloride, sodium hydroxide, agar powder, glucose and ethanol are purchased from national medicine reagents GmbH; the nano silver is purchased from Shanghai Moghai Nscience and technology limited.

Preparation example of Hypericum perforatum extract

Preparation example 1

Pulverizing 100g of herba Hyperici perforati, sieving with 60 mesh sieve to obtain coarse powder, adding 6 times of 85% ethanol solution, ultrasonic extracting for 1 hr, filtering, recovering ethanol from filtrate, and concentrating under reduced pressure to obtain extract with relative density of 1.10-1.20(60 deg.C), i.e. herba Hyperici perforati extract.

Preparation example 2

Pulverizing 100g herba Hyperici perforati, sieving with 60 mesh sieve to obtain coarse powder, adding 8 times of 80% ethanol solution, ultrasonic extracting for 2 hr, filtering, recovering ethanol from filtrate, and concentrating under reduced pressure to obtain extract with relative density of 1.10-1.20(60 deg.C), i.e. herba Hyperici perforati extract.

Examples

Example 1

The formula of the gynecological bacteriostatic gel is shown in table 1. The preparation method comprises the following steps:

dissolving ethylparaben in 10ml ethanol solution to obtain ethylparaben solution for later use;

soaking carbomer in 50g of purified water for 24 hr to swell completely to obtain carbomer gel matrix;

s2: decocting five traditional Chinese medicines of radix sophorae flavescentis, golden cypress, fructus cnidii, gallnut and safflower twice by adding water, adding 8 times of water of the medicinal materials for the first time, decocting for 2.5 hours, adding 8 times of water of the medicinal materials for the second time, decocting for 1 hour, filtering, combining filtrates of the two times, concentrating until the relative density is 1.10-1.20(60 ℃), adding ethanol to enable the alcohol content to reach 75%, stirring and uniformly mixing, taking supernate, recovering ethanol until no alcohol taste exists, and obtaining a traditional Chinese medicine extract for later use;

s3: adding the ethylparaben solution and the Chinese medicinal extract into carbomer gel matrix, adding other raw materials, stirring, adding purified water to a sufficient amount, adding triethanolamine dropwise to adjust pH to 7, mixing, and packaging to obtain 2.5 g/piece.

Examples 2 to 3

The gynecological bacteriostatic gel is different from the gynecological bacteriostatic gel in the raw material proportion shown in the table 1.

TABLE 1 raw material ratios of examples 1-3

Raw materials (g)	Example 1	Example 2	Example 3
				Sophora flavescens ait	80	85	90
Cortex Phellodendri	70	75	80
				Fructus cnidii	90	85	80
Galla chinensis	60	55	50
				Safflower carthamus	40	45	50
Oviductus ranae oil	2	1.5	1
				Plant essential oil (mint)	2	1.5	1
Glycerol	8	9	10
				Triethanolamine	10	12	15
Carbomer	10	12	15
				Nipagin ethyl ester	2	2.5	3
Benzalkonium bromide	2	1.5	1
				Purified water	624	615	604

Example 4

A gynecological bacteriostatic gel, which is different from the gel in example 2 in that the essential oil of mint is replaced by the essential oil of rose.

Examples 5 to 9

A gynecological antibacterial gel, different from example 4, further comprises nano silver with a particle size of 100nm and/or Hypericum perforatum extract prepared in preparation example 1, and purified water is reduced by corresponding weight to make the total amount of gel be 1000 g. The ratio of nano silver to hypericum perforatum extract is shown in table 2.

TABLE 2 examples 5-9 compounding ratio of nano silver and/or Hypericum perforatum extract

Example 10

A gynecological bacteriostatic gel, which is different from the gynecological bacteriostatic gel in example 6 in that the particle size of nano silver is 20 nm.

Example 11

A gynecological bacteriostatic gel, which is different from the gynecological bacteriostatic gel in example 6 in that the particle size of nano-silver is 50 nm.

Example 12

A gynecological antibacterial gel comprises the same raw materials as in example 11, and the herba Hyperici perforati extract prepared in preparation example 2 is used. The preparation method comprises the following steps:

dissolving ethylparaben in 10ml ethanol to obtain ethylparaben solution for later use;

s2: decocting five traditional Chinese medicines of radix sophorae flavescentis, golden cypress, fructus cnidii, gallnut and safflower twice by adding water, adding 10 times of water of the medicinal materials for the first time, decocting for 1.5 hours, adding 6 times of water of the medicinal materials for the second time, decocting for 2 hours, filtering, combining filtrates of the two times, concentrating until the relative density is 1.10-1.20(60 ℃), adding ethanol to enable the alcohol content to reach 75%, stirring and uniformly mixing, taking supernate, recovering ethanol until no alcohol taste exists, and obtaining a traditional Chinese medicine extract for later use;

s3: adding the ethylparaben solution and the Chinese medicinal extract into carbomer gel matrix, adding other raw materials, stirring, adding water to a sufficient amount, adding triethanolamine dropwise to adjust pH to 6, mixing, and packaging to obtain 2.5 g/piece.

Comparative example

Comparative example 1

The commercial Xiduo ylang tight gynecological gel.

Comparative example 2

Gynecological gel for treating gynecological inflammation is sold in the market.

Detection method

1. Bacteriostasis test

1.1 test sample: the gels of examples 1 to 12 and comparative examples 1 to 2 were taken as test samples 1 to 12 and control samples 1 to 2, respectively.

1.2 test strains: staphylococcus aureus (ATCC 6538), Escherichia coli (ATCC 11229), Candida albicans (ATCC 10231).

LB liquid medium: 10g of tryptone, 5g of yeast extract and 10g of sodium chloride, wherein the volume is up to 1000mL, the pH value is adjusted to 7 by using 1mol/L sodium hydroxide, and the components are subpackaged and sterilized by high-pressure steam at 121 ℃ for 20 min.

LB solid medium: adding 15g of agarose into LB liquid culture medium, subpackaging, and autoclaving at 121 deg.C for 20 min.

PDA culture medium: 200g of potatoes, 20g of glucose and 20g of agar, metering to 1000mL, subpackaging and sterilizing with high-pressure steam at 121 ℃ for 20 min.

Wherein the LB liquid culture medium and the LB solid culture medium are used for culturing staphylococcus aureus and escherichia coli, and the PDA culture medium is used for culturing candida albicans.

Selecting a ring of thalli from the thalli inclined plane after 2-3 times of activation, inoculating the thalli into a corresponding liquid culture medium, and putting the thalli into a constant-temperature oscillation incubator for culture, wherein the culture conditions of staphylococcus aureus and escherichia coli are 37 ℃ and 120 r/min; the culture conditions of Candida albicans were 28 deg.C, 150 r/min. When the bacteria grow to logarithmic growth phase, the concentration is adjusted to 5 x 10 by using a plate counting method⁵-5*10⁶cfu/mL for use.

1.3 test methods: the results of the bacteriostatic ring test according to item 2.7.2 of the Disinfection Specification (2008 edition) are shown in Table 3.

TABLE 3 results of bacteriostasis

It can be seen by combining examples 1-3 and comparative examples 1-2 and table 3 that, although the gels of comparative examples 1 and 2 also have a certain bacteriostatic effect, the gels prepared in examples 1-3 have a better bacteriostatic effect than the commercially available gels, and have better inhibitory effects on staphylococcus aureus, escherichia coli and candida albicans.

As can be seen from examples 2 and 4 in combination with table 3, the gel containing rose essential oil has a slightly better bacteriostatic effect than the gel containing mint essential oil, especially the gel has a better inhibitory effect on staphylococcus aureus, which may be due to some bacteriostatic effect of rose essential oil on staphylococcus aureus.

As can be seen by combining examples 4-9 with Table 3, the bacteriostatic effect of the gel can be improved by adding either nano-silver alone or hypericum perforatum extract alone; from example 8, it can be seen that the nano-silver has a significant inhibitory effect on staphylococcus aureus, and from example 9, the hypericum perforatum extract has a significant inhibitory effect on candida albicans; as can be seen from the comparison of examples 5 to 7 and examples 8 to 9, the bacteriostatic effect of the gel simultaneously added with nano-silver and the hypericum perforatum extract is better than that of the gel separately added with nano-silver or hypericum perforatum extract, indicating that the nano-silver and the hypericum perforatum extract have synergistic effect and the ratio of nano-silver: the weight ratio of the hypericum perforatum extract is 1: 2, the gel has the best bacteriostatic effect.

Combining examples 6, 10, 11, and 12 and table 3, it can be seen that the particle size of the nano-silver also has a certain influence on the bacteriostatic effect, the smaller the particle size of the nano-silver is, the better the bacteriostatic effect of the gel is, but when the particle size of the nano-silver is smaller than a certain degree, the difference of the bacteriostatic effect is not large, and based on the consideration of the production cost, the nano-silver with the particle size range of 20-50nm is selected.

2. Irritation test of vaginal mucosa

2.1 test samples: 2 g of the gynecological bacteriostatic gel prepared in examples 1 to 12 were respectively put into an aseptic grinding pot to be ground and mixed uniformly to obtain test samples 1 to 12, and 2 g of the gynecological gel prepared in comparative examples 1 and 2 were put into an aseptic grinding pot to be ground and mixed uniformly to obtain control samples 1 to 2.

2.2 test animals: the first-class female big-ear Japanese white rabbit provided by the laboratory animals center of the medical college of Xian transportation university weighs 2.0-2.5 kg.

2.3 test methods: according to the protocol of the vaginal mucosa irritation test, item 2.3.5 of the Disinfection Specification (2002 edition).

4 rabbits were randomly divided into experimental and control groups of 2 animals each. Before the experiment, the vaginal orifice of each animal was checked for secretions, congestion and other lesions and the catheter was connected to a 5ml syringe. Fixing the experimental rabbit on the back, exposing perineum and vaginal orifice, wetting the catheter with test solution, gently inserting the catheter into vagina for 4-5 cm, slowly injecting 2ml of test solution with a syringe, and gently withdrawing the catheter. The control group was treated with physiological saline in the same manner. After 24 hours the animals were sacrificed by air embolism, the whole vagina was removed and cut longitudinally and the mucous membrane degeneration, secretion, vascular congestion, edema were visually observed. The animal injected with physiological saline is taken as a benchmark, the conditions of mucosal degeneration, blood vessel congestion and edema are scored as 0 point, the rest animals are scored in comparison with the animal injected with physiological saline, the score is 0-5 points, the damage is more serious when the score is larger, and the test result is shown in the table 4.

TABLE 4 vaginal mucosa irritation test results

Serial number	Degeneration of mucous membranes	Congestion of blood	Swelling of the stomach
				Example 1	0	0	0
Example 2	0	0	0
				Example 3	0	0	0
Example 4	0	0	0
				Example 5	0	0	0
Example 6	0	0	0
				Example 7	0	0	0
Example 8	0	0	0
				Example 9	0	0	0
Example 10	0	0	0
				Example 11	0	0	0
Example 12	0	0	0
				Comparative example 1	1	0	1
Comparative example 2	1	0	1

As can be seen by combining examples 1-12 with comparative examples 1-2 and by combining Table 4, the gels of comparative examples 1-2 have slight swelling and mucosal degeneration phenomena in the vaginal mucosa, whereas the gynecological bacteriostatic gels prepared in examples 1-12 have no irritation to the vaginal mucosa.

The present embodiment is only for explaining the present application, and it is not limited to the present application, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present application.

Claims

1. The gynecological bacteriostatic gel is characterized by comprising the following raw materials in parts by weight:

2. The gynecological bacteriostatic gel according to claim 1, wherein the plant essential oil is rose essential oil.

3. The gynecological bacteriostatic gel according to claim 1, which further comprises 0.5-1.5 parts by weight of nano-silver and 1-3 parts by weight of hypericum perforatum extract.

4. The gynecological bacteriostatic gel according to claim 3, wherein the particle size of the nano silver is 20-50 nm.

5. The gynecological bacteriostatic gel according to claim 3, wherein the preparation method of the hypericum perforatum extract comprises the following steps: pulverizing herba Hyperici perforati, sieving to obtain coarse powder, adding 6-8 times of 80-85% ethanol solution, ultrasonic extracting for 1-2 hr, filtering, recovering ethanol from filtrate, and concentrating under reduced pressure to obtain extract with relative density of 1.10-1.20(60 deg.C), i.e. herba Hyperici perforati extract.

6. The gynecological bacteriostatic gel according to claim 3, wherein the weight ratio of the nano-silver to the hypericum perforatum extract is 1: 2.

7. a process for preparing a gynaecological bacteriostatic gel according to any one of claims 1 to 6, comprising the steps of:

8. The preparation method of the gynecological bacteriostatic gel according to claim 7, wherein the specific conditions of adding water and decocting twice in S2 are as follows: adding 8-10 times of water for the first time, decocting for 1.5-2.5 hr, adding 6-8 times of water for the second time, decocting for 1-2 hr, and filtering.