WO2007033591A1

WO2007033591A1 - Active prosthetic material for wounds

Info

Publication number: WO2007033591A1
Application number: PCT/CN2006/002459
Authority: WO
Inventors: Shanshan Xi
Original assignee: Shanshan Xi
Priority date: 2005-09-22
Filing date: 2006-09-20
Publication date: 2007-03-29
Also published as: CN1935267A; CN100502953C

Abstract

An active prosthetic material for wounds is mainly composed of hyaluronic acid, silicon dioxide, sodium oxide, calcium oxide and phosphorous pentoxide. The active prosthetic material for wounds can promote the movements of epidermic cells and fibroblasts, reduce circulating resistance in newborn blood vessels, hinder the deposition of granulocytes, restrain swelling of vascular endothelium, decrease accretion of cell debris in vessels, and extremely reduce resistance of blood and incidence of embolism in micrangiums, thereby it can improve local microcirculation and tissue repair, has the effect of promoting growth of the blood vessel. The prosthetic material can be applied to treat diabetic ulcers, bedsores, depressed ulcers, skin and mucous membrane ulcers and vesicant diseases, local a or b burns and scalds, various wounds caused by operation and trauma, the wounds which cann’t be sutured at phase I, the surgical incisions which haven’t healed in an ideal period, cervical erosions, wounds healing after healing of hansens disease, and the wounds which are hard to heal for unknown reason.

Description

Wound active repair material

The present invention relates to a material for treating wounds, and more particularly to a wound repairing material for treating wounds.

Background technique

In the prior art, the dressings used for treating wounds can be divided into traditional dressings, animal dressings, synthetic dressings, biological dressings, drug dressings and fixed dressings according to materials and uses. The research on dressings has been very recent in the past decade. Great progress, but the prior art dressing, 1. Can not absorb the wound exudate well, maintain the wound temperature, provide a good local environment for wound healing, actively promote wound healing; 2. Can not maintain the proper amount of blood circulation in the wound And oxygen, inhibiting vascular endothelial swelling, which hinders blood vessel growth; 3. Especially the prior art dressings for treating diabetic ulcers, hemorrhoids, burns, gynecological cervical erosion, wound healing after healing of leprosy and unexplained causes The wounds that are difficult to heal, the healing effect is poor, and the cure rate is very low; the wound healing caused by the prior art is slow and long-lasting, which brings great pain to the patient, both physically and physically, and also increases The expenditure on medical expenses has brought many inconveniences to patients.

Summary of the invention

The object of the present invention is to provide a wound active repair material, which can effectively promote blood vessel growth, improve local microcirculation of damage, promote cell proliferation and growth factor expression, promote wound healing and reduce scar by the repair material of the present invention. Formed to compensate for the deficiencies in the prior art.

The wound active repairing material of the invention is mainly composed of the following components:

Hyaluronic acid, silicon dioxide, sodium oxide, calcium oxide, phosphorus pentoxide.

The main components are composed of the following weight ratios: Hyaluronic acid 3-40%;

Silica 20-45%;

Sodium oxide 6-20%;

Calcium oxide 8-25%;

Phosphorus pentoxide 2 - 7 %.

The composition of the wound active repairing material proposed by the invention is stable, and the silica, sodium oxide, calcium oxide, and phosphorus pentoxide are mixed and pulverized, the particle diameter is not more than 300 um, and then mixed with hyaluronic acid in proportion. The post-made wound-repairing material can be made into powder, paste and plug by reworking.

The wound active repairing material of the invention can be used for treating diabetic ulcer acne pressure ulcer, skin and mucosal ulcer and erosive lesion localized degree III degree burn and scald, various surgical and surgical wounds, can not be sutured in stage I. Wounds, surgical incisions that failed to heal on time, gynecological cervical erosion, wound healing after healing of leprosy, unhealthy wounds caused by unknown causes.

In one embodiment of the invention, its main components are comprised of the following weight ratios:

Hyaluronic acid 30%;

Silica 33%;

Sodium oxide 16%;

Calcium oxide 18%;

Phosphorus pentoxide 3 %.

The wound active repairing material of the present invention, because of its unique surface activity, can increase the local oxygen pressure and pH value when it contacts the soft tissue wound surface, and form a strong surface negative charge, adsorbing fibrin, collagen and Cells, which promote the rapid formation of calcium and phosphorus layers, stabilize these proteins and cells in the wound, and promote wound healing. In order to verify the effect and effect of the above-mentioned wound active repairing material, the patent applicant of the present invention was approved by a relevant state department of the country and carried out in a medical university affiliated hospital in China. Clinical validation.

The clinical observations are summarized as follows:

1. Case selection -

(1) Case selection criteria

1 indications: A skin mucosal or soft tissue ulcerative lesions; B skin mucosal erosive lesions; C can not be sutured wounds in stage I, surgical incisions that fail to heal on time; localized 11 degree and 111 degree burns or burn wounds ;

2 The age is 12-85 years old, both in the outpatient and inpatient, male or female.

(2) Case elimination criteria

1 The observation period is less than 4 weeks;

2 In the observation period, use other methods to change the drug.

2. Test method -

(1) The selected cases were divided into the experimental group and the control group. The age, condition and wound condition of the two groups were similar. In cases with multiple wounds, one wound can be selected for treatment observation, and other wounds can be changed according to the conventional method, and self-control can be used.

(2) Wound treatment

1 test group: disinfection of the wound surface according to the conventional method, remove dirt and necrotic tissue, and cover the wound active repair material, change once a day or every other day; insulin can be placed in the wound of diabetic patients, other patients according to the situation of the wound Enter gentamicin, or saline wet dressing, or oil gauze drainage; etc.; the wounds were evaluated at 72 hours, 1 week, 2 weeks, 3 weeks, and 4 weeks after the first use of the material.

2 Control group: According to the above method, the drug was applied without wound wound repair material, and the wound evaluation time was the same as that of the test group.

3 observation period: 4 weeks.

4 During the observation period, other special external medicines for granulation growth cannot be used, but the wounds can be properly debrided according to the situation. 3. Observation indicators

(1) Wound exudate: no secrets 0, a little exudate +, obvious exudate ++.

(2) Wound granulation tissue: no meat growth, granulation dark atrophy or pale edema, granulation red, fine granules easily bleed.

(3) Velocity growth rate: The growth rate of granulation is calculated according to the change of wound depth and expressed as a percentage.

(4) Wound healing rate: Calculate the healing rate according to the degree of wound area reduction, using the percentage table

(5) Check blood routine, liver and kidney function, plasma protein and blood glucose before and at the end of observation.

4. Efficacy criteria: The efficacy is divided into four levels: recovery, markedly effective, effective, and ineffective.

(1) Healing: The wound is completely healed;

(2) markedly effective: wound exudates, fresh granulation, growth rate and healing rate greater than 60 ° /. .

(3) Effective: The wound surface is slightly exuded, the granulation is fresh, and the growth rate and healing rate are 20-60%.

(4) Invalid: The wound surface is obvious, no granulation growth or granulation is not fresh, and the growth rate and healing rate are less than 20%.

5. Adverse reaction criteria

During the observation period, the patient's main complaints were assessed as positive, relevant, affirmative, irrelevant, and incapable of evaluation.

6. Test results

(1) Case selection

50 cases were enrolled in the study, and 43 cases in the experimental group, 2 of which were eliminated after 4 weeks of observation, 41 cases were actually completed in the test group, and 7 cases were in the control group.

41 patients in the experimental group, with an average age of 49.9 years; 7 patients in the control group, with an average age of 48.7 years. The basic conditions of the two groups of cases are shown in Tables 1 to 5. Gender distribution in both groups

Table 2 Age distribution of two groups of cases

The primary etiology of the two groups of patients analyzed the primary disease test group control pemphigus and infection 6 1 vasculitis 2

Diabetes 6 2 Surgery or wound healing 5 2 Drug allergy 5 1 Burns 4

Hemorrhoids 3

Electric burn 2

Infection 1

Eczema 1

Hot crushing 1 1 systemic lupus erythematosus 1

Unknown reason 4 Wound area (cm ² ) Wound depth (cm) Test group 22.97 0. 75 Control group 10. 75 0. 55 Bacterial culture results of wounds in two groups

Table 7 granulation tissue in wounds

Table 8 Comparison of growth rate of granulation tissue in wounds

72 hours IS

丄 ·< 2 weeks 3 weeks 4 weeks n % ri % n % n % n %

11 26.8 36 87.8 35 97.2 19 100 17 100 Inspection 20%

Group

0 0 1 14.3 6 85.7 6 785.7 6 100

60%

Correct

0 0 1 14.3 6 85.7 6 85.7 6 100 Photo 20%

Group

0 0 0 0 0 0 3 42.9 4 66.7

60% (2) treatment effect

1 Wound exudate: After 72 hours of treatment, the exudate of the wound surface decreased, and it decreased significantly after 1 week. The comparison effect is shown in Table 6.

2 wound granulation tissue situation

The granulation tissue of the wound began to grow in 72 hours, and the fresh granulation tissue increased after 1 week. See Table 7 for comparison with the control group.

3 granulation tissue growth rate

After 72 hours of treatment, the granulation tissue of the wound began to grow. After 1 week, the growth rate was faster, which was obviously better than that of the control group, as shown in Table 8.

4 wound healing rate

After 72 hours, the wound area of the wound-repairing material began to shrink, and the shrinking speed was the fastest in 2 weeks, and the speed became stable after 2 weeks. In the control group, the wound area began to shrink at 1 week, accelerated at 3 weeks, and reached the test group level at 4 weeks, as shown in Table 9.

Wound area reduction

72 hours 1 week 2 weeks 3 weeks 4 weeks n % n % n % n % n %

13 31.7 26 63.4 32 88.9 18 90.0 17 100 Test 20%

Group

1 2.4 13 31.7 22 61.1 12 60.0 11 64.7

60%

Correct

0 0 2 28.6 7 100 7 100 6 100 Photo 20%

Group

0 0 0 0 0 0 3 42.9 4 66.7

60% 5 clinical efficacy

According to the standard of the treatment plan, the recovery rate of the test group was 9.8% at 1 week, and 46.3% at 2 weeks. Another case was cured after the second stage suture, accounting for 56.1% at 3 weeks. Zhou Shizhan accounted for 75.6%. In the control group, the wounds did not heal within 2 weeks. The cure rate accounted for 14.3% at 3 weeks, and 42.9 at 4 weeks, which was significantly lower than the test group. According to the effective recovery + marked effect, the total efficacy of the two groups is shown in Table 10. .

(adverse reaction situation

No serious adverse reactions were found in this group of patients. Only one patient with circumcision had local pain after wound-recovery material, and was relieved with the reduction of the amount of topical wound-repairing material, and no other adverse reactions. There were no obvious abnormal changes in the laboratory test indicators before and after the test, as shown in Table 11. Comparison of clinical effects between the two groups

The invention proves that the wound active repairing material of the present invention can promote the healing of soft tissue wounds, the total effective rate is 82.9%, the wound healing rate is 75.6%, and the marked efficiency is 7.3%; The repair material can significantly reduce the wound exudate and promote the growth of granulation tissue. After using this material, more than 64.9% of the cases have fresh granulation tissue, and after 6 weeks, more than 69.4% of the cases, granulation growth rate More than 60%; in the healing of soft tissue wounds, the cure rate was 9.8% at 1 week, 46.3% at 2 weeks, and 3 weeks 56. 1%, accounting for 75.6% at 4 weeks, which is obviously better than the conventional dressing method of the control group; the present invention has not found any toxic side effects in the experiment, and the wound active repairing material of the present invention has the effect of promoting the healing of soft tissue wounds. Significant therapeutic effect without any side effects.

Typical case 1

Patient XXX Female 45 years old, suffering from pemphigus vulgaris, half a year, erythema of the whole body, blisters with erosion, obvious exudation, visible oral mucosa, extensive flaky erosion of the gingival area with infection, severe pain, can not eat, difficult Enduring; externally applied wound repairing material, once a day, pain relief after one week, wound granulation tissue is fresh, oozing is reduced, skin lesions are significantly reduced, pain is significantly reduced after two weeks, and the wound is completely dry and healed.

Typical case 2

Patient XXX Male 54 years old due to fever, redness and swelling on the back for half a month, intravenous antibiotics, poor effect, hospitalized in February 1998, on the back of the examination, there was 18 X 10cra ² size redness and swelling, fluctuation, test white blood cells 19. 1 X 10 ⁹ / L, fasting blood glucose 13. 5nimol / L, diagnosis of diabetes and back edema, incision and drainage, the first 5 days of exudate more purulent, conventional dressing plus wound active repair material, starting on the 6th day The exudate was reduced. At the same time, the wound surface was sprayed with hydrogen peroxide and the wound surface active repairing material was applied. The patient's wound surface became fresher, the granulation tissue grew faster, the suture was broken after two weeks, and the wound was discharged after 4 weeks.

Typical case 3

Patient XXX Male 12 years old, in 1996, he was treated for 6 hours after electrical contact injury. He was admitted to the hospital. The surface of the fifth metacarpal head of the right palm had a burn wound of 3 X4cm ² and the lateral calf of the right lower leg was burned 6 X 12cm ^{2 .} , the head of the right sac area of the head scalp III degree burn, 6 days after the right palm, right calf sputum skin grafting, head III degree wound sputum, wound ll X 20cm ² , deep periosteum, skull exposed 5 X 6cm ² exudation Obviously, the external wound healing material was started 1 day after operation, and the material was changed once every 1-3 days according to the wound condition. After 1 week, there was a little granulation tissue growth at the exposed cranial margin. After 2 weeks, the exudate was significantly reduced, and the pH value was increased. High, the granulation tissue growth rate reached 37.5%, the wound healing rate was 22.73%, because the water infusion of the implant dilator was insufficient, so The scalp wound continued to use wound-repairing materials, and the growth rate of granulation tissue reached 100°/ after 4 weeks. . Table 11 Laboratory test results

Typical case 4

Patient XXX, female, 73 years old, was hospitalized for 19 days after cerebral hemorrhage. The patient was found to be comatose in the bathroom 22 days ago. The skin on the back shoulder and buttocks was burned and crushed. After the hospital, the dressing was routinely changed, but the wound was never After that, it was changed to regular dressing plus SDAg external application, oil yarn drainage, the effect was not good, after 30 days of admission, the topical wound active repair material was changed, and the wound became more The speed of the joint was obviously accelerated, the wound on the right shoulder was not deep, the wound was completely healed in 4 weeks, the wound on the buttocks was deep, and the granulation color was dark. The granulation tissue was fresh after 1 week of wound dressing repair material plus regular dressing change, and the growth was faster. After 4 weeks The wound healing was more than 85%, which was significantly better than the conventional method of dressing change without any adverse reactions.

Typical case 5

XXX, male, 65 years old, due to the skin of the foreskin glans collapsed for 2 months, check: the back of the glans has a 0. 8 X 1. 5cm ² ulcer, the inner root of the foreskin has a 2. 0 X 0. 5cm ² ulcers, ulcer depth 0. 2cm, used 1: 5000PP external washing and oral PPA and other anti-inflammatory drugs, the effect is not obvious, after the use of wound active repair materials, once a day, after 3 days, the exudate disappeared, the wound began to shrink, At 1 week, the granulation tissue was fresh, the wound surface was reduced by 50%, and the ulcer was completely healed at 2 weeks without any adverse reactions.

The wound active repairing material of the invention can stimulate the migration, proliferation and differentiation of epidermal cells and fibroblasts, thereby satisfying the requirements of rapid synthesis of matrix and epidermal cover, reducing the circulation resistance of newly repaired blood vessels, hindering the deposition of granulocytes, It inhibits vascular endothelial swelling, reduces the accumulation of cell debris in blood vessels, greatly reduces the blood resistance of blood vessels and the incidence of embolism, thereby improving local microcirculation, tissue repair, promoting blood vessel growth, and the formation of blood vessels for the regeneration of regenerative tissues. Further differentiation in morphology and function plays an important role; wound active repair materials can be used to treat diabetic ulcers, acne, pressure ulcers, skin and mucosal ulcers and erosive lesions, localized degree II and degree burns and Wounds caused by burns, various operations and trauma, wounds that cannot be sutured in stage I, surgical incisions that failed to heal on time, gynecological cervical erosion, wound healing after healing of leprosy, and wounds that are difficult to heal due to unexplained causes.

In a second embodiment of the invention, the main components thereof are composed of the following weight ratios:

Hyaluronic acid 3%

Silica 45%;

Sodium oxide 20%; Calcium oxide 25%;

Phosphorus pentoxide 7%.

Clinical observations are as follows - typical case 6

Patient XXX 60-year-old man with right lower leg ulcer due to diabetes, with an area of 2 X12 cm ² and a depth of 0.5 cm. After treatment with the above formula, healed after 6 weeks of treatment.

Typical case 7

Patient XXX 44-year-old man with scrotal ulcer caused by taking anti-cold medicine, the area is 3Xlcm ² , the depth is 0.3cm, the course of disease is 3 days, and healed after 4 weeks of treatment with the above formula.

Typical case 8

Patient XXX 37-year-old male due to drug allergy caused glans skin erosion, area 3 X3cm ² , depth 0.2cm, with the above formula products after 4 weeks of treatment after recovery.

In a third embodiment of the invention, the main components thereof are composed of the following weight ratios:

Hyaluronic acid 40%

Silica 28%;

Sodium oxide 20%;

Calcium oxide 10%;

Phosphorus pentoxide 2 ° /. .

The clinical observations are as follows:

Typical case 9

Patients XXX 66-year-old man with left external hemorrhoid due to diabetes, an area of 3 X cm ² , a depth of 15 cm, a course of 3 months, treated with the above formula products after 6 weeks of healing.

Typical case 10

Patient XXX 34 Male due to drug allergy caused by glans erosion, area 1.5X.0cm ² , depth 0.1, duration of 1 week, after treatment with the above formula products for 4 weeks痊 More.

Typical case 11

Patient XXX 65-year-old male with glans ulcer due to unknown cause, 2 lesions, area 1.5X0.6cm ² and 2.0X0.5cm ² , depth 0.2cm, cured after 4 weeks of treatment with the above formula products.

Typical case 12

Patient XXX 73 Female had a right shoulder ulcer due to burns after accidental fainting. The area was 3X5cm ² , the depth was lcm, and the course of disease was 54 days. The product of the above formula was cured 6 weeks after treatment.

The wound active repairing material of the invention can be made into a powder form, a paste form and a plug shape, and the powder form is a white fine powder, and no impurities visible to the naked eye are required; the paste is white and tasteless; the plug is a white duck. Mouth plug.

Claims

Rights request

1. A wound active repair material consisting mainly of the following components:

The wound active repairing material according to claim 1, wherein the main component is composed of the following weight ratios:

3-40%;

20-45%;

6-20%;

8-25%;

2-7 %.

The wound active repairing material according to claim 1, wherein the material has a powder form, a paste form or a plug shape.

The wound active repairing material according to claim 1 or 2, wherein: the silica, the sodium oxide, the calcium oxide, and the phosphorus pentoxide in the repairing material are mixed and pulverized, and the particle diameter thereof is not more than 300 um, then mixed with hyaluronic acid to make a wound-active repair material.