CN112156173A - Gel for treating pelvic floor muscle dysfunction and preparation method thereof - Google Patents

Abstract

The invention discloses a gel for treating pelvic floor muscle dysfunction and a preparation method thereof, which solve the problem that the existing exercise therapy and drug therapy for treating pelvic floor muscle dysfunction have disadvantages, and the gel comprises the following components in mass concentration: and (3) extracting the curcuma zedoary: 0.5% -1.5%; soybean isoflavone: 0.05% -0.5%; boswellic acid: 0.05 to 0.5 percent; fibronectin: 0.02% -0.1%; hydrolyzing collagen: 0.1% -1%; the balance of auxiliary materials. According to the technical scheme, the components are reasonably matched, beneficial substances are greatly reserved in the preparation process, and the components are mutually promoted; can be absorbed by mucous membrane after vaginal administration, promotes the contraction of pelvic floor muscle tissue, repairs muscular nerves, improves the tension of muscles, realizes the treatment of pelvic floor dysfunction, and has remarkable effect on improving stress urinary incontinence caused by pelvic floor injury.

Description

Gel for treating pelvic floor muscle dysfunction and preparation method thereof

Technical Field

The invention relates to the field of biological medicines, and particularly relates to a gel for treating pelvic floor muscle dysfunction and a preparation method thereof.

Background

Female pelvic floor muscles are divided into two parts, namely superficial muscles which mainly give the superficial transverse perineal muscles, and deep muscles which mainly give the levator ani muscles. The main component of the superficial muscle is type II muscle fiber, which mainly plays a role in staged contraction, and is a fast-contraction fiber, which has the functions of autonomous contraction and reflex maintenance, and is easy to fatigue. The deep muscle mainly comprising levator ani muscle is mainly made of I-type fiber, mainly plays a role in tension contraction, is a slow contraction fiber, can maintain tension for a long time, and is not easy to fatigue. In the human body, the main role of the pelvic floor musculature is to maintain the normal function and structure of the pelvic floor. Women are likely to cause pelvic floor muscle damage during pregnancy and childbirth. For example, mechanical damage of levator ani muscles occurs easily during vaginal delivery of women, especially pelvic floor muscles are greatly damaged by factors such as perineum tearing, instrumental delivery assistance, overweight of fetus, long second stage of labor and the like, and pelvic floor dysfunction diseases are caused. Pelvic floor dysfunctional diseases refer primarily to diseases resulting from dysfunction, injury, degeneration or defect of pelvic support structures, most commonly including female genital tract injury, stress urinary incontinence, pelvic organ prolapse, and the like.

At present, the pelvic floor muscle dysfunction is mainly treated by means of pelvic floor muscle rehabilitation training. The pelvic floor muscle exercise refers to the conscious voluntary contraction exercise of the pelvic floor muscle group, mainly the pubococcygeus muscle group, by the patient. Pelvic floor nerve can be changed by pelvic floor muscle exercise, and muscle contraction strength and tension are strengthened. At present, pelvic floor muscle rehabilitation therapy mainly comprises (1) Kegel exercise, which is used for recovering the function of the pelvic floor and enhancing the supporting effect of the pelvic floor muscle on pelvic tissues through pelvic floor muscle exercise; (2) the pelvic floor muscle rehabilitation exercises are based on Kegel exercises and set 4 groups of exercises for hip, hip twisting, whole body and anus lifting according to physiological conditions of different stages of a puerpera. (3) Pelvic floor electrical stimulation therapy, which is to stimulate pelvic floor muscle groups with low voltage by using vaginal electrodes; (4) acupuncture therapy, in which acupuncture manipulations such as twirling and lifting and inserting are used to stimulate specific parts of the human body under the guidance of the theory of traditional Chinese medicine, is achieved by burning and fumigating moxibustion herbs on certain points of the body surface and utilizing thermal stimulation to treat diseases. Although the above methods are reported to have certain therapeutic effects on pelvic floor muscle dysfunction, the treatment progress is slow, the rehabilitation training actions are monotonous, no fixed contact mode exists, the patients cannot stand well due to the monotonous action in the contact process, urine leaks out when a great number of patients do rehabilitation actions due to urine leakage, and once the progress is slow, even the exercise is stopped, the compliance of the patients is poor.

Besides rehabilitation exercise, drug therapy should be combined with pelvic floor function rehabilitation training to achieve better rehabilitation treatment effect because of its convenient use and good patient compliance. Research proves that the traditional Chinese medicine preparations such as Guifu Dihuang Wan and Buzhong Yiqi Wan can effectively improve the symptom of pelvic floor dysfunction by combining with pelvic floor physical rehabilitation therapy, and the treatment effect is better than that of simple pelvic floor rehabilitation therapy, but the molecular treatment mechanism of the method is not clear and the curative effect is unstable. In addition, there are also clinical operations in which estrogen or phytoestrogen (such as pueraria root or soybean isoflavone) is administered to improve pelvic floor muscle function, especially the symptoms of stress urinary incontinence. However, the medicine thickens vaginal mucosa through the stimulation effect of estrogen, but has no treatment effect on the injury of pelvic floor muscles.

Disclosure of Invention

In order to solve the defects, the invention provides the gel for treating the pelvic floor muscle dysfunction and the preparation method thereof, and the gel can be absorbed by mucous membranes after vaginal administration, so that the contraction of pelvic floor muscle tissues is promoted, the muscular nerves are repaired, the tension of muscles is improved, and the treatment of the pelvic floor dysfunction is realized.

The above object of the present invention is achieved by the following technical means: the gel for treating pelvic floor muscle dysfunction is characterized by comprising the following components in mass concentration:

and (3) extracting the curcuma zedoary: 0.5% -1.5%;

soybean isoflavone: 0.05% -0.5%;

boswellic acid: 0.05 to 0.5 percent;

fibronectin: 0.02% -0.1%;

hydrolyzing collagen: 0.1% -1%;

the balance of auxiliary materials.

The curcuma zedoary extract has the function of promoting the contraction of pelvic floor muscles and is beneficial to recovering the contraction function of the pelvic floor muscles. The curcuma zedoary extract adopted by the invention is an alcohol extract, and researches show that the curcuma zedoary extract has a remarkable contraction promoting effect on pelvic floor muscles. The action effect is mediated by alpha adrenergic receptors and M choline receptors of pelvic floor muscle cells respectively. The zedoary turmeric extract has alpha adrenergic receptor agonist function, and can promote pelvic floor muscle contraction to improve pelvic floor muscle function. Meanwhile, the curcuma zedoary extract has an M choline receptor exciting function and further strengthens the contraction effect of the flat bottom muscle.

The soybean isoflavone in the invention is phytoestrogen, has partial estrogen function, but does not produce related side effects. The sensitivity of alpha adrenergic receptor can be further improved by the action of the soybean isoflavone estrogen-like substance, and the stimulation effect of the zedoary turmeric extract on pelvic floor muscle contraction is enhanced.

Beta boswellic acid in the frankincense has a neuroprotective effect, and the effect is to protect nerves by (1) stimulating cells to secrete neurotrophic factor (NGF); (2) boswellic acid has the effect of repairing nerve injury by promoting axon growth. Pelvic floor muscle damage can lead to pelvic floor muscle peripheral nerve damage, and the denervation of pelvic floor muscle leads to muscle contraction function decline, leads to pelvic floor muscle relaxation, therefore effectual repair pelvic floor muscle nerve damage can promote the recovery of pelvic floor muscle function.

The fibronectin and the hydrolyzed collagen are extracellular matrix components and exist in the interstitial substance of cells, and the fibronectin and the collagen are used together, so that the fibronectin and the collagen can promote muscle cells to secrete extracellular matrix proteins such as collagen, and the like, thereby repairing pelvic floor muscle injury.

Preferably, the auxiliary materials comprise the following components in percentage by mass:

carbomer: 0.2% -1%;

glycerol: 2% -10%;

propylene glycol: 1% -10%;

methyl paraben: 0.05% -0.3%;

propyl p-hydroxybenzoate: 0.05% -0.3%;

triethanolamine: 0.2% -1%;

the balance of deionized water.

A preparation method of gel for treating pelvic floor muscle dysfunction comprises the following steps:

weighing corresponding mass of the curcuma zedoary extract, the boswellic acid and the soybean isoflavone, and uniformly dispersing the three raw materials by using propylene glycol to obtain a mixture A;

weighing carbomer powder and hydrolyzed collagen with corresponding mass, adding into deionized water, adding glycerol, heating to 80 deg.C, stirring and dissolving completely to obtain mixture B;

when the temperature of the mixture B is reduced to 45 ℃, adding fibronectin, methyl paraben and ethyl paraben while stirring, and obtaining a mixture C;

adding the mixture A into the mixture C under the condition of 45 ℃, uniformly stirring, and homogenizing for 2 minutes at the homogenizing speed of 1000 revolutions per minute, namely obtaining a mixture D;

and adding triethanolamine into the mixture D, and fully and uniformly stirring to form a gel final product.

A gel for treating pelvic floor muscle dysfunction and a preparation method thereof, the components are reasonably matched, beneficial substances are greatly reserved in the preparation process, and the components are mutually promoted; can be absorbed by mucous membrane after vaginal administration, promotes the contraction of pelvic floor muscle tissue, repairs muscular nerves, improves the tension of muscles, realizes the treatment of pelvic floor dysfunction, and has remarkable effect on improving stress urinary incontinence caused by pelvic floor injury.

Detailed Description

The present invention will be described in more detail with reference to examples.

Example 1

A gel for treating pelvic floor muscle dysfunction and its preparation method are provided, wherein 0.5 g of Curcumae rhizoma extract, 0.1 g of boswellic acid and 0.1 g of soybean isoflavone are weighed, and 9.3 g of propylene glycol is used to disperse the three raw materials uniformly to obtain a mixture A;

weighing 1 g of carbomer U20 powder and 0.5 g of hydrolyzed collagen, adding into 82.1 g of deionized water, adding 5g of glycerol, heating to 80 ℃, and stirring to dissolve fully, so as to obtain a mixture B;

when the temperature of the mixture B is reduced to 45 ℃, adding 0.1 g of fibronectin, 0.15 g of methyl hydroxybenzoate and 0.15 g of ethyl hydroxybenzoate into the system while stirring, and obtaining a mixture C;

adding the mixture A into the mixture C under the condition of 45 ℃, uniformly stirring, and homogenizing for 2 minutes at the homogenizing speed of 1000 revolutions per minute, namely obtaining a mixture D;

then 1 g of triethanolamine is added to the mixture D, and the gel end product is formed after the mixture D is fully and evenly stirred.

Filling the gel final product into a vaginal push tube, wherein each tube contains 3 g of gel;

the gel is pushed into vagina by the patient with pelvic floor dysfunction by the push tube, and the pelvic floor function can be recovered once a day or every other day.

The mass percentages of the components in the embodiment are as follows: 0.5 percent of zedoary extract; soybean isoflavone 0.1%; 0.1% of boswellic acid; fibronectin 0.1%; 0.5% of hydrolyzed collagen; 1% of carbomer; 5% of glycerol; 9.3 percent of propylene glycol; 0.15 percent of methylparaben; 0.15 percent of propyl paraben; triethanolamine 1% and deionized water 82.1%.

Efficacy evaluation

1. In vitro muscle contraction evaluation

As the pelvic floor muscle contraction function has no corresponding animal model, the duodenum smooth muscle is taken as an experimental object, and inflammatory products have influence on the contraction performance of the 12 rectum smooth muscle and have the effect on alpha receptors.

The experimental scheme is as follows: the rats were fasted for 16 hours, anesthetized and killed by cervical dislocation, the rats were opened at their abdomens, the intestinal tracts were cut from the junction between the pylorus and duodenum of the stomach, cut into sections of about 1cm, gently washed with Kirschner fluid, placed in Kirschner fluid, humidified at a constant temperature of 37 ℃ and adjusted to a base tension of 1 g, and mixed gas (950 mL. L. -1 oxygen and 50 mL. L. -1 carbon dioxide) was continuously introduced into the ventilation hook at a rate of 1 to 2 bubbles per second. Contraction activity and change signals of the small intestine smooth muscle are led to a multi-channel physiological signal acquisition and processing system of a BL-420 biological function experiment through a tension transducer. The leaching liquor of the product of the embodiment with the mass ratio of 0.01%, 0.1%, 1% and 10% is respectively added into the Kirschner solution, and the observation and search curve is repeated for 6 times. Then after stabilization, 0.5% prazosin was added and the shrinkage curve was continued.

The results show that the contraction degree of the Kirschner fluid added with 0.01% of the product leaching solution has no significant difference with that of the negative control Kirschner fluid, namely 3.2 +/-1.1 nm and 3.6 +/-0.9 nm, but the contraction degree of the smooth muscle after the 0.1%, 1% and 10% of the leaching solution is significantly different with that of the desktop solution, and the contraction degree is dose-dependent and is respectively 5.5 +/-0.7 nm, 7.9 +/-1.4 nm and 9.2 +/-2.2 nm. Addition of 0.5% prazosin showed that all contractile groups were inhibited, as respectively (1) bench top: 4.6 +/-1.3 nm; (2) 0.01% product leach liquor + 0.5% prazosin: 0.7 plus or minus 0.2; (3) 0.1% product leach liquor + 0.5% prazosin: 0.6 +/-0.2 nm; (4) 1% product leach liquor + 0.5% prazosin: 1.4 +/-0.4 nm; (5) 10% product leach liquor + 0.5% prazosin: 2.1 +/-0.6 nm. The above results indicate that the product extract has the ability to promote smooth muscle contraction and that this effect can be blocked by alpha receptor blockers, indicating that its ability to promote smooth muscle contraction is mediated through alpha receptors.

2. Small-scale clinical experiment for treating pelvic floor muscle injury

To objectively evaluate the repair effect of the products on the pelvic floor muscle function, we summoned 20 patients with pelvic floor muscle damage due to pregnancy and childbirth, which is manifested by the phenomenon of typical stress urinary incontinence.

The severity of urinary incontinence was assessed objectively using a 1h urine pad test: during the test, the bladder was filled for 1h, and the patient did not urinate any more from the beginning of the test. A weighed pad (e.g., sanitary napkin) is pre-placed. The patient drinks 500ml of plain boiled water within 15min from the beginning of the test; then, the patient walks up and down the steps of the 1 st floor for 30 min. Finally, 15min, the patient should sit upright 10 times, cough 10 times, run in place for 1min, pick up the objects on the ground 5 times, and wash with tap water for 1 min. At the end of the test, the pad is weighed, the patient is asked to urinate and the urine volume is measured. Positive results showed that the urine leakage was not less than 2 g. Mild: the urine leakage is less than or equal to 2g and less than 5 g; medium: the urine leakage is less than or equal to 5g and less than 10 g; and (3) severe degree: the urine leakage is more than or equal to 10g and less than 50 g; extremely severe: the urine leakage is more than or equal to 50 g. Patients with mild and very severe disease were excluded from the study.

Each patient used the product 1 time a day for 18 consecutive days, and the test was performed every 6 days. The repairing effect of pelvic floor muscles was observed. The results showed 13 patients with severe disease (65%), 7 patients with moderate disease (35%), 6 patients with severe disease (30%), 8 patients with moderate disease (40%), 5 patients with mild disease (25%), and 1 patient with turning to the negative (5%) out of 20 patients before the start of the experiment; after 12 days of use 3 patients with severe disease (15%), 3 patients with moderate disease (15%), 8 patients with mild disease (40%), and 6 patients with turning negative (3%); after 18 days of use, 2 patients were severe (10%), 2 patients were moderate (10%), 7 patients were mild (35%), and 9 patients were turned to negative (45%).

The results showed that the product had a significant effect on 19 of the 20 patients during the experimental period, and thus the product had a significant effect on improving stress urinary incontinence due to pelvic floor injury.

The products within the mass concentration range of each component in the claims of the invention can produce corresponding effects, and the examples are not given by way of illustration.

Claims (3)

1. The gel for treating pelvic floor muscle dysfunction is characterized by comprising the following components in mass concentration:

and (3) extracting the curcuma zedoary: 0.5% -1.5%;

soybean isoflavone: 0.05% -0.5%;

boswellic acid: 0.05 to 0.5 percent;

fibronectin: 0.02% -0.1%;

hydrolyzing collagen: 0.1% -1%;

the balance of auxiliary materials.

2. The gel for treating pelvic floor muscle dysfunction according to claim 1, wherein the auxiliary materials comprise the following components in percentage by mass:

carbomer: 0.2% -1%;

glycerol: 2% -10%;

propylene glycol: 1% -10%;

methyl paraben: 0.05% -0.3%;

propyl p-hydroxybenzoate: 0.05% -0.3%;

triethanolamine: 0.2% -1%;

the balance of deionized water.

3. The method for producing a gel for the treatment of pelvic floor muscle dysfunction according to claim 1 or 2, wherein:

weighing corresponding mass of the curcuma zedoary extract, the boswellic acid and the soybean isoflavone, and uniformly dispersing the three raw materials by using propylene glycol to obtain a mixture A;

weighing carbomer powder and hydrolyzed collagen with corresponding mass, adding into deionized water, adding glycerol, heating to 80 deg.C, stirring and dissolving completely to obtain mixture B;

when the temperature of the mixture B is reduced to 45 ℃, adding fibronectin, methyl paraben and ethyl paraben while stirring, and obtaining a mixture C;

adding the mixture A into the mixture C under the condition of 45 ℃, uniformly stirring, and homogenizing for 2 minutes at the homogenizing speed of 1000 revolutions per minute, namely obtaining a mixture D;

and adding triethanolamine into the mixture D, and fully and uniformly stirring to form a gel final product.