WO2017185596A1

WO2017185596A1 - Polyhexamethylene guanidine medicament for treating gastrointestinal diseases, method for preparing same and use thereof

Info

Publication number: WO2017185596A1
Application number: PCT/CN2016/099708
Authority: WO
Inventors: 卫国刚
Original assignee: 卫国刚
Priority date: 2016-04-25
Filing date: 2016-09-22
Publication date: 2017-11-02
Also published as: CN105726491A

Abstract

The invention relates to a polyhexamethylene guanidine medicament for treating gastrointestinal diseases. The final polyhexamethylene guanidine medicament is prepared by using polyhexamethylene guanidine as an active component, and adding starch, glucose, lactose, microcrystalline cellulose and magnesium stearate in an appropriate weight ratio. The medicinal preparation can be used to treat the gastrointestinal diseases in human bodies in the form of a liquid, powder, particle, tablet or capsule.

Description

Polyhexamethylene guanidine medicine for treating gastrointestinal diseases and preparation method and application thereof

Technical field

The invention belongs to the technical field of medicines, and in particular relates to a polyhexamethylene guanidine medicine for treating gastrointestinal diseases, a preparation method and application thereof.

Background technique

In the prior art, drugs for treating gastrointestinal diseases caused by bacteria, viral infections such as diarrhea, acute and chronic gastroenteritis, superficial gastritis, gastric ulcer, etc. are sulfonamides, quinolones, ciprofloxacin hydrochloride, and oxygen. Antibiotics such as flaroxacin, amoxicillin, and gentamicin sulfate participate in the cell metabolism of bacteria and viruses by means of effective drug components in antibiotics, and disturb or inhibit cell metabolism, thereby achieving sterilization purposes. After being taken by the human body, these drugs enter the blood and lymph through the visceral mucosal epithelial cells, and are widely distributed and remain in various tissues, thereby exerting toxic and side effects on the normal tissues of the human body while acting on the lesions. In addition, long-term use of these drugs will lead to resistance to various types of bacteria, fungi, and viruses, affecting the bactericidal effect and therapeutic effect.

Polyhexamethylene oxime, environmentally friendly polymer, has a broad spectrum of sterilization, low effective concentration, fast action, stable nature, and good solubility in water. It can be used at room temperature, long-term antibacterial, no side effects, no corrosive, colorless, odorless, non-toxic, non-combustible, non-explosive, safe to use, moderate in price, convenient to transport, and a very effective fungicide. It is currently widely used in the sterilization of medical devices, public environments, home, fabrics, food, milk, and care products. At present, there are no reports on the use of polyhexamethylene hydrazine in the treatment of gastrointestinal diseases in China.

Summary of the invention

In order to solve the above problems existing in the prior art, the present invention provides a polyhexamethylene guanidine drug for treating gastrointestinal diseases with rapid onset, good curative effect, no toxic side effects, no residual in the body, and no drug resistance. Preparation methods and applications. The pharmaceutical preparations can treat human gastrointestinal diseases in the form of liquids, powders, granules, tablets or capsules.

The technical solution adopted by the invention is:

A polyhexamethylene guanidine drug for treating gastrointestinal diseases, the raw material components include:

Polyhexamethylene hydrazine, 0.1-15 parts by weight;

Starch, 12.5-18 parts by weight;

Glucose, 25-35 parts by weight;

Lactose, 40-45 parts by weight;

Microcrystalline cellulose, 2-8 parts by weight;

Magnesium stearate, 1-4 parts by weight.

Further preferably, the raw material components of the polyhexamethylene oxime drug for treating gastrointestinal diseases include:

Polyhexamethylene hydrazine, 2-10 parts by weight;

Starch, 15-16 parts by weight;

Glucose, 28-32 parts by weight;

Lactose, 42-44 parts by weight;

Microcrystalline cellulose, 4-6 parts by weight;

Magnesium stearate, 2-3 parts by weight.

The polyhexamethylene hydrazine is one or more of polyhexamethylene gluconate gluconate, polyhexamethylene hydrazine lactic acid, polyhexamethylene sulfonium sulfate, and polyhexamethylene phosphide phosphate. A mixture of proportions.

The polyhexamethylene hydrazine is polyhexamethylene ruthenium gluconate, polyhexamethylene hydrazine lactic acid, polyhexamethylene sulfonium sulfate, and polyhexamethylene phosphite phosphate according to a mass ratio of 2-8:2- A mixture of 8:2-8:2-8.

The starch is a mixture of one or more of corn starch, tapioca starch, and potato starch in any ratio.

The glucose is anhydrous glucose; anhydrous glucose, that is, glucose containing no crystal water, is a colorless crystal or a white crystalline powder, is odorless, sweet, soluble in water, and slightly soluble in ethanol.

The microcrystalline cellulose is silicified microcrystalline cellulose; the silicified microcrystalline cellulose is obtained by blending microcrystalline cellulose and colloidal silica in water and drying at 105 ° C for 30 min, and the microcrystalline cellulose should be 94 wt%. -99.9 wt%.

A method for preparing the polyhexamethylene oxime drug for treating gastrointestinal diseases, comprising the steps of:

(1) separately weigh each raw material component, mix well and obtain a mixture, and add 2-5 times of mass water to the mixture to be beaten to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a drug granule;

(3) After the granules of the step (2) are dried, the polyhexamethylene oxime drug for treating gastrointestinal diseases is obtained.

In the step (2), the particle diameter of the drug granule is 50-200 μm, so that the granule can be directly prepared, or the medicinal granules satisfying the requirements can be tableted by a tableting machine to obtain a polyhexamethylene oxime drug tablet. The agent may also be directly divided into capsules according to a certain amount to obtain a polyhexamethylene oxime drug capsule. It should be noted that, according to the innovative idea of the present invention, combined with the conventional pharmaceutical preparation formula, it is easy to be expanded and applied: the compound liquid of polyhexamethylene hydrazine drug can be applied to oral ulcer spray, eye drops, ear drops Gynecological lotion; polyhexamethylene guanidine drug can also be used to prepare various gynecological gels or gynecological suppositories; polyhexamethylene guanidine drugs can also be used to prepare creams for treating athlete's foot or skin diseases.

In the step (3), the drying temperature is 80-120 ° C, and the drying time is 30-240 min.

The polyhexamethylene oxime drug is used in the preparation of a medicament for treating gastrointestinal diseases.

The beneficial effects of the invention are:

The polyhexamethylene oxime drug for treating gastrointestinal diseases according to the present invention, by using polyhexamethylene hydrazine as a medicinal component, and adding a suitable ratio of starch, glucose, lactose, microcrystalline cellulose and hard Magnesium oleate, the final preparation of polyhexamethylene hydrazine drug, enters the gastrointestinal tract and directly interacts with the pathogen, attracts and envelops the pathogen through positive and negative charges, cuts off the nutrient intake channel of the pathogen and effectively inhibits the division of the pathogen And the polymer film formed by polyhexamethylene hydrazine can block the respiratory passage of the pathogen and cause the bacteria to quickly suffocate and die; according to the above treatment mechanism, first, the polyhexamethylene hydrazine is not directly involved in the cell metabolism of the pathogenic cells. Effectively avoiding the use of antibiotics in the prior art, which easily leads to the resistance of various pathogens, thereby affecting the bactericidal effect and therapeutic effect; further, since polyhexamethylene oxime is used as a macromolecular polymer, it will not be digested. Absorption of tube mucosal epithelial cells, thereby avoiding the use of antibiotics in the prior art, which tends to cause drug components to remain in various tissues, In addition, the polyhexamethylene oxime has a strong covering protection ability on the digestive tract mucosa, repairs and improves the defense function of the mucosal barrier against the attack factor, and has a balanced normal flora and local analgesic effect. In summary, the polyhexamethylene oxime drug of the present invention does not have resistance to various bacteria, fungi and viruses by means of a special sterilizing mechanism, and the bactericidal effect is not affected by bacteria, fungi or viruses. The effect is quick on action and good in curative effect. The polyhexamethylene sulfonium drug enters the body and is not absorbed by the cells, and is directly excreted through the stomach and intestines, and does not remain in the body, and has no toxic and side effects.

detailed description

The invention will now be described in detail in connection with specific embodiments.

In the following examples, 1 g is represented by 1 part by weight.

Example 1

The present embodiment provides a polyhexamethylene guanidine drug for treating gastrointestinal diseases, and the raw material components include:

Polyhexamethylene gluconate gluconate, 0.1 parts by weight;

Corn starch, 18 parts by weight;

Anhydrous glucose, 25 parts by weight;

Lactose, 45 parts by weight;

Microcrystalline cellulose, 2 parts by weight;

Magnesium stearate, 4 parts by weight.

(1) separately weigh each raw material component, thoroughly mix and mix to obtain a mixture material, and add 2 times of mass water to the mixture to be beaten to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a drug particle having a particle diameter of 50 μm;

(3) After the granules of the step (2) are dried at 80 ° C for 240 minutes, the polyhexamethylene oxime drug for treating gastrointestinal diseases can be obtained.

Example 2

a mixture of polyhexamethylene gluconate and polyhexamethylene ruthenate in a mass ratio of 2:8, 15 parts by weight;

Tapioca starch, 12.5 parts by weight;

Anhydrous glucose, 35 parts by weight;

Lactose, 40 parts by weight;

Microcrystalline cellulose, 8 parts by weight;

Magnesium stearate, 1 part by weight.

(1) separately weigh each raw material component, mix well and obtain a mixture, and add 5 times of mass water to the mixture to be beaten to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a drug particle having a particle diameter of 200 μm;

(3) After the granules of the step (2) are dried at 120 ° C for 30 minutes, the polyhexamethylene oxime drug for treating gastrointestinal diseases can be obtained.

Example 3

a mixture of hexamethyl hydrazine gluconate, polyhexamethylene hydrazide lactic acid, polyhexamethylene sulfonate sulfate in a mass ratio of 2:2:8, 2 parts by weight;

Potato starch, 16 parts by weight;

Anhydrous glucose, 28 parts by weight;

Lactose, 44 parts by weight;

Silicified microcrystalline cellulose, 4 parts by weight;

Magnesium stearate, 3 parts by weight.

(1) separately weigh each raw material component, thoroughly mix and mix to obtain a mixed material, and add 3.5 times of mass water to the mixed material for beating treatment to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a drug particle having a particle diameter of 150 μm;

(3) After the granules of step (2) are dried at 100 ° C for 120 minutes, the gastrointestinal diseases can be treated. Diseased polyhexamethylene guanidine drug.

Example 4

a mixture of hexamethyl hydrazine gluconate, polyhexamethylene hydrazide, polyhexamethylene sulfonate, and polyhexamethylene phosphite in a mass ratio of 2:8:2:8, 10 parts by weight;

Corn starch, 15 parts by weight;

Anhydrous glucose, 32 parts by weight;

Lactose, 42 parts by weight;

Silicified microcrystalline cellulose, 6 parts by weight;

Magnesium stearate, 2 parts by weight.

(1) separately weigh each raw material component, mix well and obtain a mixture, and add 4 times of mass water to the mixture to be beaten to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a granule having a particle diameter of 100 μ;

(3) After the granules of the step (2) are dried at 110 ° C for 60 minutes, the polyhexamethylene oxime drug for treating gastrointestinal diseases can be obtained.

Example 5

a mixture of hexamethyl hydrazine gluconate, polyhexamethylene hydrazine lactic acid, polyhexamethylene sulfonate sulfate, and polyhexamethylene phosphite phosphate in a mass ratio of 8:2:8:2, 8 parts by weight;

Corn starch, 15.5 parts by weight;

Anhydrous glucose, 30 parts by weight;

Lactose, 43 parts by weight;

Silicified microcrystalline cellulose, 5 parts by weight;

Magnesium stearate, 2.5 parts by weight.

(3) After the granules of the step (2) are dried at 110 ° C for 80 minutes, the polyhexamethylene oxime drug for treating gastrointestinal diseases can be obtained.

Experimental example

The present inventors observed the polyhexamethylene oxime drug of the present invention for 100 patients with clinical gastrointestinal diseases, including 52 males and 48 females, the youngest being 19 years old, the largest being 78 years old, and 23 cases of acute gastroenteritis. There were 42 cases of gastric ulcer and 35 cases of gastrointestinal symptoms.

How to use:

Treatment of diarrhea: twice daily, 0.4-0.6 grams each time, taking 1-3 days;

Treatment of gastroenteritis, gastric ulcer: twice daily, 0.4-0.6 grams each time, taking 3-7 days.

Efficacy evaluation criteria:

Cure: Clinical symptoms disappeared completely, 71 cases.

Effective: clinical symptoms improved significantly, 27 cases.

Invalid: There were no significant improvement in symptoms and signs in 2 cases. The total effective rate is 98%.

Typical clinical cases:

Song, female, 52 years old, not long ago, stomach upset, swollen face, stool test blood, do gastroscopy pathological analysis, the diagnosis is that there are stomach ulcers and atrophic gastroenteritis, hanging water more than 20 days after discharge, never How long does it take for the edema of the face and the symptoms of fecal bleeding again? After using the polyhexamethylene guanidine drug of the third embodiment of the present invention for 3 days, the condition is improved, and after 4 days of use, it is cured, and so far there is no gastric ulcer or atrophic gastritis. relapse.

Wang, female, 39 years old, had a stomach bleeding a week ago, and the stool was black. After gastroscopy, it was a gastroduodenal ulcer, acute gastroenteritis, and stomach bleeding. He was discharged after hospital treatment. However, the patient still had a complex face, pale hands and feet, dizziness, headache, and did not want to eat after leaving the hospital. After taking the polyhexamethylene guanidine drug of the fourth embodiment of the present invention for 2 days, the patient's symptoms of discomfort were improved, and after 5 days of continuous treatment, the patient was cured, and the patient's gastroduodenal ulcer, acute gastroenteritis, stomach bleeding No more recurrence, no symptoms of pale complexion, pale hands and feet, dizziness, headache, and no want to eat.

The present invention is not limited to the above-described preferred embodiments, and any other form of product can be derived by anyone of the present invention, but without any change in shape or structure, it is the same as or equivalent to the present application. Approximate technical solutions are all within the scope of the present invention.

Claims

A polyhexamethylene oxime drug for treating gastrointestinal diseases, characterized in that the raw material components include:

Polyhexamethylene hydrazine, 0.1-15 parts by weight;

Starch, 12.5-18 parts by weight;

Glucose, 25-35 parts by weight;

Lactose, 40-45 parts by weight;

Microcrystalline cellulose, 2-8 parts by weight;

Magnesium stearate, 1-4 parts by weight.
The polyhexamethylene oxime drug for treating gastrointestinal diseases according to claim 1, wherein the raw material component comprises:

Polyhexamethylene hydrazine, 2-10 parts by weight;

Starch, 15-16 parts by weight;

Glucose, 28-32 parts by weight;

Lactose, 42-44 parts by weight;

Microcrystalline cellulose, 4-6 parts by weight;

Magnesium stearate, 2-3 parts by weight.
The polyhexamethylene oxime drug for treating gastrointestinal diseases according to claim 1, wherein the polyhexamethylene hydrazine is polyhexamethylene gluconate gluconate, polyhexamethylene ruthenium citrate, sulfuric acid A mixture of one or more of polyhexamethylene sulfonium and polyhexamethylene phosphite phosphate in any ratio.
The polyhexamethylene guanidine drug for treating gastrointestinal diseases according to claim 1, wherein The polyhexamethylene hydrazine is polyhexamethylene ruthenium gluconate, polyhexamethylene hydrazine lactic acid, polyhexamethylene sulfonium sulfate, and polyhexamethylene phosphite phosphate according to a mass ratio of 2-8:2- A mixture of 8:2-8:2-8.
The polyhexamethylene oxime drug for treating gastrointestinal diseases according to claim 1, wherein the starch is a mixture of one or more of corn starch, tapioca starch, and potato starch in an arbitrary ratio.
The polyhexamethylene oxime drug for treating gastrointestinal diseases according to claim 1, wherein the glucose is anhydrous glucose.
The polyhexamethylene oxime drug for treating gastrointestinal diseases according to claim 1, wherein the microcrystalline cellulose is silicified microcrystalline cellulose.
A method for preparing a polyhexamethylene oxime drug for treating gastrointestinal diseases according to any one of claims 1 to 7, characterized in that it comprises the following steps:

(1) separately weigh each raw material component, mix well and obtain a mixture, and add 2-5 times of mass water to the mixture to be beaten to obtain a slurry;

(2) granulating the slurry of the step (1) to obtain a drug granule;

(3) After the granules of the step (2) are dried, the polyhexamethylene oxime drug for treating gastrointestinal diseases is obtained.
The preparation method according to claim 8, wherein in the step (2), the particle size of the drug particles is 50-200 μm;

In the step (3), the drying temperature is 80-120 ° C, and the drying time is 30-240 min.
Use of the polyhexamethylene guanidine drug according to any one of claims 1 to 7 for the preparation of a medicament for the treatment of gastrointestinal diseases.