WO2011011214A1

WO2011011214A1 - A pharmaceutical composition for the treatment of open wounds

Info

Publication number: WO2011011214A1
Application number: PCT/US2010/041650
Authority: WO
Inventors: Guanghua Chen
Original assignee: PINECREST INTERNATIONAL CORP Ltd
Current assignee: PINECREST INTERNATIONAL CORP Ltd
Priority date: 2009-07-21
Filing date: 2010-07-12
Publication date: 2011-01-27
Anticipated expiration: 2012-01-21

Abstract

A pharmaceutical composition that can be used at all stages of the healing process for open wounds comprises: (a) an anti- infection/antimicrobial composite, (b) a tissue regeneration composite, and optionally a pharmaceutically acceptable diluent or excipient; wherein the weight ratio of the anti- bacterial/antimicrobial composite and the tissue regeneration composite varies from approximately 3:1 to approximately 1:1; preferably from approximately 2.5:1 to approximately 1.5:1. Process of preparation and method of application are also described.

Description

A PHARMACEUTICAL COMPOSITION FOR THE TREATMENT OF OPEN WOUNDS

FIELD OF THE INVENTION

This invention relates to a pharmaceutical composition for treating open wounds .

OTHER REFERENCES:

The Merck Manual 18th Edition, 2006, Mark H. Beers (Author), Robert S. Porter (Editor), Thomas V. Jones (Editor) pp. 985, 1011, 2548, 2592-2596.

The Merck Manual of Medical Information, 1999, Robert Berkow. http : //www.merckmedicus . com/ppdocs/us/hcp/content/schlossberg/ chapters/schlossberg-ch-094-s002. htm

Acute and Chronic Wounds: Nursing Management, 2000, Routh Bryant (Editor), second Edition.

Clinical Manual of Emergency Pediatrics, 2002, E. Crain, J. Gershel. (Edition fourth).

Singer AJ, Clark RA. Cutaneous wound healing. N Engl J Med. 1999;341 (10) :738-746

Resident Orientation Manual, Feb. 2000, Produced by Galveston Shriners Burn Hospital and the University of Texas Medical Branch Blocker Burn Unit.

Comparison of chronic wound care products. Pharmacist's Letter.

2008;24 (5) :240511.

Chinese Materia Medica, Shanghai Science and Technology Press, 2006

Pharmacopoeia of the People's Republic of China 2005

The Pharmacopoeia of the People's Republic of China (PPRC), compiled by the Pharmacopoeia Commission of the Chinese Ministry of Public Health, is an official compendium of drugs, covering Traditional Chinese and western medicines, and giving information on the standards of purity, description, test, dosage, precaution, storage, and the strength for each drug. It is recognized by the World Health Organization as the official Chinese pharmacopoeia.

BACKGROUND

There are two types of wounds: acute wounds and chronic wounds . Acute wounds include burnt wounds and traumatic wounds. Chronic wounds include pressure sores and diabetic sores. Every year in the United States more than 6.5 million have chronic skin ulcers caused by pressure, venous stasis, or diabetes mellitus. In addition, each year, more than 2 million Americans require treatment for burns, and between 3,000 and 4,000 die from severe burns. Burns can be assessed in terms of total body surface area (TBSA) . It is especially challenging to treat patients whose TBSA exceeds 10% in an adult, or 5% in young children or elderly. One reason is because in normal skin, epidermis (outermost layer) and dermis (inner or deeper layer) exist in a steady-stated equilibrium, forms a protective barrier against the external environment. Damaged skin and other body surfaces are easily infected because they can no longer act as a barrier against invading organisms. Depending on the location affected and the degree of severity, a burn victim may experience a wide number of potentially fatal complications including shock, infection, electrolyte imbalance and respiratory distress. Beyond physical complications, burns can also result in severe psychological and emotional distress due to scarring and deformity.

The classic model of wound healing is divided into four sequential, yet overlapping phases: (1) homeostasis, (2) inflammatory, (3) proliferative, and (4) remodeling. Traditionally, medical practitioners have applied different medicine and/or methods to treat each phase separately. The consideration and goals for these four phases include:

(1) Homeostasis phase: stopping bleeding, relieving pain, preventing and/or treating infection; (2) Inflammatory phase: debridement, moisture protection, managing infection, wound protection, packing (for deep wounds);

(3) Proliferative (Granulation) phase: improving microcirculation, controlling exudates, packing (for deep wounds ) ;

(4) Remodeling/maturation phase: wound protection and scar prevention and treatment.

Although progresses have been made in medicine and methods for treating each phase, medical professionals still face challenges in many areas. For example, infection is still a very serious risk during treating the inflammatory phase stage and could be lethal for patients with severe burns. Those patients often must be kept in a special unit. All medical treatments must follow extremely strict aseptic procedures to make sure patients do not get infections. Antibiotics and non-steroid anti-inflammatory drugs (NSAIDs) are also necessary in order to prevent and/or control infection. Furthermore, although skin grafting is typically applied in the proliferative phase to achieve better healing effect, nevertheless, this option is usually not available for patients with large TBSA. Medical doctors have to rely on alternative methods such as artificial skin (i.e. scaffolds of collagen) with transplanted fibroblast cells to regenerate new dermis layer, since dermis does not regenerate naturally under normal circumstances. These techniques require a long healing period, very high overall expense, and the newly generated skin does not look like or function as the natural skin (i.e. scar, no hair pore, no sweating, lacking sensory nerves, etc.) . Also, additional skin grafting is usually needed during the remodeling/maturation phase to regenerate the epidermis layer. Skin grafting requires multiple surgery, is expensive and a pain to go through. Chinese medical literatures have recorded that many herbs exhibit therapeutic effects to skin wounds. Many researchers have therefore, tried different herbal compositions to treat damaged skin.

US Patent No. 5,405,608 to Rongxiang Xu discloses the extraction of Huangqin, Huanglian, Huangbai, earthworms, poppy seeds, and beeswax to sesame oil.

US Patent No. 5,766,614 to Yong Liu discloses the use of Chinese pharmaceuticals including rhubarb, calcium hydroxide, sanguisorba officinalis rhizome, common camphor, coptis chinensis rhizome, phellodendron amurense bark and oldenlandia diffusa roxd.

US Patent No. 6,447,820 to Sarfaraz K Niazi discloses a treatment of existing and prevention of new skin scars in humans and animals using a topical application containing alcoholic extracts of Cortex Phellodendri and Opuntia ficus indica in a specific combination.

US Patent No. 6,555,118 to Sarfaraz K Niazi discloses a pharmaceutical composition for the treatment of wounds and ulcers in humans and animals and a method of preparation of the same composition is also provided. The composition consists of an alcoholic extract of Huangqin, Huanglin, Huangbai, Opuntia, Dilong, and beta-sitosterol (from soybean extract), in a vegetable oil-wax base, from where the alcohol is essentially removed by evaporation.

US Patent application Pub. No. US 2003/0190379 Al, dated Oct. 9, 2003 from Du Ben Hai discloses the use of a finer mixture of healing agents which consists of Radix Scutellariae, Cortex Phellodendri, Rhizoma Coptidis according to the ratio by weight of 1:1:1. Those herbal compositions have exhibited encouraging advantages over the existing therapeutic methods. Nevertheless, many disadvantages have also been observed. Some compositions do not possess a strong anti- infection/antimicrobial property and frequent cleaning and dressing change (every 4 to 6 hours) are required to prevent infection. Frequent dressing change would slow down skin regeneration process and cause pain and inconvenience to patients. Scar tissues are often observed due to the prolonged healing process. Some compositions cannot effectively promote the growth of blood vessel in the newly generated dermis layer, a process which usually takes 2 - 4 weeks under normal conditions. Without blood vessels carrying the immune system's infection fighting machinery, bacteria can easily grow, cause infection, and destroy the newly grown skin. Therefore, an improved composition is needed.

SUMMARY OF THE INVENTION

It is an objective of this invention to provide a pharmaceutical composition which can be used at all stages of the healing process for open wounds. The composition can provide multiple medical effects that assist the entire healing process, including stop bleeding, pain relief, anti- inflammation, prevention and treatment of infection, and fostering of new soft tissue growth.

It is another objective of this invention to provide a composition with potent anti-microbial qualities for a broad spectrum of wound pathogens including bacterial, virus, and fungus. The improved anti-microbial qualities would greatly simplify the complicate task of selecting appropriate antibiotics in the long healing process.

It is another objective of this invention to reduce the efforts required to clean up the wound and/or replace the dressing by reducing the frequency of dressing changes.

It is another objective of this invention to minimize scars or contractures formation and minimize skin grafting required for the patients after the healing of the soft tissues.

In summary, the invention discloses an unique pharmaceutical composition for treating open wounds, such as traumatic wounds, burns, ulcers, etc., which comprises: (a) an anti- infection/antimicrobial composite, (b) a tissue regeneration composite, and optionally a pharmaceutically acceptable diluent or excipient; wherein the weight ratio of the antibacterial/antimicrobial composite and the tissue regeneration composite varies from approximately 3:1 to approximately 1:1; preferably from approximately 2.5:1 to approximately 1.5:1. Process of preparation and method of application are also described.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1: A flow chart of a process for preparing the ointment form of a pharmaceutical composition.

Figure 2: A baby hand (Volar side) with burn wound, before the treatment with the pharmaceutical composition.

Figure 3: A baby hand (Dorsal side) with burn wound, before the treatment with the pharmaceutical composition.

Figure 4: A baby hand (Volar side) after treatment with the pharmaceutical composition.

Figure 5: A baby hand (Dorsal side) after the treatment with the pharmaceutical composition.

DETAILED DESCRIPTION OF THE INVENTION

After reviewing hundreds of Chinese medical literatures, combined with extensive experiments, the inventor has discovered that some herbal composites exhibited extraordinary effects in assisting wound healing. For example, Daihuang and Huzhang have been observed improving the microcirculation of blood in the wounded area. Sanqi and Xuejie possess phenomenal functions to stop bleeding and to relieve pain. In addition, Sanqi relieves the local inflammatory symptom by reducing the secretion of mucus from the damaged tissue. Bailian, Daihuang, Huzhang, and Moyao improves the nutrition supply in dermis layer, which subsequently stimulate the growth of new cells. When properly treated, the newly grown skin looks and functions more like normal skin, rarely leaving scars, keloids, or contracture after healing.

The inventor has recognized that the skin healing process should be viewed as a dynamic whole process. Instead of isolating the various stages and treating each stage step by step, this invention provides a composition suitable for the entire healing process. Inspired by the four stages of the skin healing process, the inventor has recognized that the anti-infection/antimicrobial stage and the tissue regeneration stage are closely related and interacting with each other. An effective composition must possess strong anti- infection/antimicrobial properties, and at the same time, strong tissue regeneration/tissue proliferation properties. When herbs were properly combined together, they can greatly promote the regeneration of new tissue (including epidermis, dermis, and certain deeper body structures, such as fat, fascia, blood vessel, nerves, hair pores, and muscle) and quickly fill up the wound. The pharmaceutical composition disclosed in this application dramatically improves the traditional methods of treating skin wounds. The invention leads to the following advantages: faster and better healing of the wounds, great relieves to the patients, and dramatically reduced overall medical cost. The treatment minimizes the need for further plastic surgery. These advantages were considered more significant for patients with severe burns .

The inventor has carefully selected two groups of herbs, namely an anti-infection/antimicrobial composite, and a tissue-regeneration composite. The anti- infection/antimicrobial composite is selected from Bailian, Chuanxiong, Daihuang, Haiercha, Huangbo, Huanglian, Huangqin, Huzhang, Sijiqing, Zicao, and Zhizi (Please see detailed descriptions provided below for each herb.). The tissue regeneration composite is selected from Bailian, Daihuang, Duyebaiji, Haiercha, Huzhang, Chuanxiong, Moyao, Ruxiang, Sanqi, Sijiqing, and Xuejie (Please see detailed descriptions provided below for each herb.) . Each of the herbal ingredient exhibits a strong anti-infection/antimicrobial quality, or a potent tissue proliferation/ regeneration quality, or both. When properly combined together, the compositions disclosed in this invention have exhibited a phenomenal effect in expediting the skin healing process. The combination of anti- infection/antimicrobial and tissue regeneration composite can greatly suppress inflammation and infections caused by pathogens, and improve blood microcirculation and nutrition supplies in the wounded area. According to the feedbacks from patients to whom the compositions were applied, the compositions disclosed in this invention also have phenomenal pain-relieving effect.

This invention provides a pharmaceutical composition for treating skin wounds which comprises: (a) an anti- infection/antimicrobial composite, (b) a tissue regeneration composite. The anti-infection/antimicrobial composite is selected from two or more of Bailian, Chuanxiong, Daihuang, Haiercha, Huangbo, Huanglian, Huangqin, Huzhang, Sijiqing, Zicao, and Zhizi. The tissue regeneration composite is selected from two or more of Bailian, Daihuang, Duyebaiji, Haiercha, Huzhang, Chuanxiong, Moyao, Ruxiang, Sanqi, Sijiqing, and Xuejie. Additional herbal ingredients may be included in case of special needs for treatment. For example, in circumstances where patients are suffering from great pain, the composition may further comprise Bingpian. The composition may also comprise one or more pharmaceutically acceptable excipients including MiIa (serving as a filler/binder in semi-solid formulation such as ointment, paste and gel) .

It is important to select at least two herbal ingredients from the anti-infection/anti-bacterial composite, and at least two different ingredients from the tissue-regeneration composite. In some preferred embodiments, three or more herbal ingredients from the anti-infection/anti-bacterial composite are selected. Different herbal ingredients often exhibit complementary pharmaceutical functions through different mechanisms. When combined together, the ingredients synergize with each other and greatly enhance the overall effect. For example, herbs such as Chuanxiong, Haiercha, Huzhang, Huanglian, Sijiqing and Zicao all exhibit certain anti-infection/antibacterial effects at in-vitro and/or in- vivo conditions. Yet the combination of Chuanxiong and Huzhang show much stronger anti-infection/anti-bacterial quality and could effectively kill Pseudornonas aeruginosa which is a common reason of infection in burned wound. The combination of Sijiqing and Zicao could prevent the growth of Escherichia coli (E. coli) , another major cause of serious infection. The combination of Huzhang and Zicao exhibits an enhanced anti-infection property which combats a variety of drug-resistant bacteria (such as Pseudomonas aeruginosa, etc.). When combined together, the final anti-infection/antibacterial composite used in this invention kills and/or prevents the growth of a broad spectrum of wound pathogens: bacterial, virus, and fugal, precluding the complicate task of selecting the antibiotics in the multi-stage healing process.

Traditionally, open wounds needed to be cleaned daily, or more frequently, to remove the dead cells and mucus generated by the inflamed tissue, and to prevent infection. The frequent clean-up was very painful for the patients, and the cleaning procedures were also harmful for the newly regenerated dermis tissues. When the combined dose of Daihuang, Huzhang, Ruxiang, and Sanqi, is applied, it helps to control the local inflammation and reduce the mucus excretion, leading to less frequent clean-ups and dress changing. For minor to moderate open wounds, patients do not need to change dressing in three days. For severe open wounds, patients do not need to change dressing more than once a day. This modification helps to preserve the newly regenerated dermis cells/tissues, thus, accelerates the healing process. It certainly reduced the patients' agony too.

The detailed description for each herbal ingredient is as follows .

Bailian (RADIX AMPELOPSIS) used in the invention is selected from Ampelopsis japonica (Thunb.) Makino. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Bingpian (Borneol, BORNEOLUM SYNTHETICUM) used in the invention is from the resin of Dryobalanops aromatica Gaertn.f ., family Dipterocarpaceae, or chemically synthesized from camphor and turpentine oil. (Pharmacopoeia of the People's Republic of China, 2005)

Chuanxiong (RHIZOMA CHUANXIONG) used in the invention is selected one or more from the group of Ligusticumchuanxiong Hort or Ligusticumwallichii Franch. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Daihuang (RADIX ETRHIZOMARHEI ) used in the invention is selected one or more from the group of RheumpalmatumL and RheumtanguticumMaxim exBalf and RheumofficinaleBaill . The root is used (Pharmacopoeia of the People's Republic of China, 2005) .

Duyebaiji. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

MiIa (BEESWAX, FENGLA) Beeswax is a natural wax secreted by Apis cerana Fabricius or Apis mellifera Linnaeus. (Fam. Apidae). (Pharmacopoeia of the People's Republic of China, 2005)

Haiercha (CUTCH, BLACK CATECHU) used in the invention is selected from ACACIA CATECHU (L. F.) Willd. (Fam. Leguminosae) . The decoction of the branch and stem is used. (Pharmacopoeia of the People's Republic of China, 2005).

Huangbo (CORTEX PHELLODENDRI ) used in the invention is selected one or more from the group of Phellodendronchinense Schneid and Phellodendronamurense Rupr . The bark is used. (Pharmacopoeia of the People's Republic of China, 2005) Huanglian (RHIZOMA COPTIDIS) used in the invention is selected one or more from the group of Coptischinensis Franch, Coptis deltoidea C.Y.Cheng et Hsiao, and Coptisteeta Wall. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Huangqin (RADIX SCUTELLARIAE) used in the invention is selected from Scutellariabaicalensis Georgi . The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Huzhang (RHIZOMA POLYGONI CUSPIDATI) used in the invention is selected from the group of Polygonumcuspidatum Sieb.et Zucc. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Moyao (MYRRH) used in the invention is selected from CommiphoramyrrhaEngl . [C .molmolEngl . ] The resin is used. (Pharmacopoeia of the People's Republic of China, 2005)

Ruxiang (FRANKINCENSE) used in the invention is selected one or more from the group of Boswelliacarterii Birdw. [B . sacraFluek . ] , B .bhawdajianaBirdw . , and B. neglecta M.Moore. The resin is used. (Pharmacopoeia of the People's Republic of China, 2005)

Sanqi (RADIX NOTOGINSENG) used in the invention is selected one or more from the group of Panaxnotoginseng (Burk.) F.H.Chen. The root is used. (Pharmacopoeia of the People's Republic of China, 2005)

Sijiqing (SIJIQING) used in the invention is selected from Ilexchinensis Sims. The root skin, leaves, and seeds are use. (Pharmacopoeia of the People's Republic of China, 2005). Xuejie (SANGUIS DRAXONIS) used in the invention is selected one or more from Daemonoropsdraco Blume . The resin is used. (Pharmacopoeia of the People's Republic of China, 2005)

Zicao (RADIX ARNEBIAE) used in the invention is selected from Arnebiaeuchroma (Royle) Johst . The root is used (Pharmacopoeia of the People's Republic of China, 2005)

Zhizi (FRUCTUS GARDENIAE) used in the invention is selected from Gardeniajasminoides ElIi. The fruit are used. (Pharmacopoeia of the People's Republic of China, 2005)

All herbal ingredients may be processed using common methods disclosed in Pharmacopoeia of the People's Republic of China 2005. According to the reference, "Chinese Materia Medica, Shanghai Science and Technology Press, 2006," none of these pharmaceutical components are toxic. Also, according to the Pharmacopoeia of the People's Republic of China (PPRC 2005), no toxic effect has been observed for any of the herbal ingredients associated with topical use.

In preparation of the pharmaceutical composition, each individual herbal ingredient counts from approximately 5% to approximately 25% of the total weight of all raw herbal materials. Moreover, when the total weight of the antibacterial/antimicrobial composite is compared to the total weight of the tissue regeneration composite, the ratio could vary from approximately 3:1 to approximately 1:1, preferably from approximately 2.5:1 to approximately 1.5:1.

Some raw materials may be first cut or grinded in order to provide more surface area prior to dissolution and extraction. This procedure is especially important for seeds or chunky raw material such as Bailian, Baizhi, Chuanxiong, Daihuang, Huangbo, Huanglian, Huzhang and Zhizi. Subsequently, the raw materials (grinded and unprocessed) are mixed thoroughly. The mixture may be soaked and heated in solvents (i.e., vegetable oil or oil mixtures) to dissolve/extract the hydrophobic active ingredients present in the raw materials. The weight ratio of the solvent versus the total herbal mixture being extracted is from approximately 10:1 to approximately 2.5:1. The time required for dissolution and extraction varies, depending upon the different composites. The temperature is usually controlled in the range of 80 to 150 ⁰C. The mixture is separated by filtration, and the liquid phase was collected. If necessary, more herbs and/or excipients, such as Bingpian, Xuejie, Ruxiang, Sanqi, and Zicao, may be grinded into fine powder and added directly into the liquid phase. This mixture could be further formulated into various semisolid formulations such as ointment, paste and gel, when MiIa is used as a filler/binder in these formulations. The weight of MiIa could be up to 30% of the mixture.

The raw materials in this invention may be processed by water extraction, alcohol extraction, or oil extraction. The ingredients can also be dissolved or suspended in a liquid to form a liquid formulation, prepared into a spray formulation, dried and mixed with solid carriers for a powder formulation, and dispersed or emulsified in a medium in a conventional manner or mixed with a semi-solid (gel) to form a paste, ointment, cream, lotion or the like for easy application to the skin. The choice of the final form may be decided in terms of convenience.

For the purpose of this invention, pharmaceutically acceptable diluents or excipients mean any of the standard pharmaceutical diluents or excipients which are well-known in the art. Examples of suitable pharmaceutically acceptable diluents or excipients may include, but not limited to, purified water, alcohols, polyols, vegetable oil, petroleum jelly (Vaseline), paraffin and ozocerite wax, natural and synthesized polymers such as xanthanes, gelatin, microcrystalline cellulose, collagen, starch, and the like. Methods for formulating those carriers are well-known in the art.

Example 1 :

Materials used:

Bingpian: 2 kg

Huanglian: 4 kg

Huzhang: 2 kg

MiIa: 16 kg

Ruxiang: 2kg

Sanqi: 2 kg

Vegetable oil: 100kg

Zicao: 4 kg

All materials were selected according to the quality standard described in Pharmacopoeia of PRC (PPRC 2005)

Procedures of Preparation:

(1) Cutting Zicao, Huzhang, and Huanglian into pieces and then soaking the said pieces in vegetable oil at room temperature for three days,

(2) Heating the mixture of vegetable oil and the said pieces in step (1) up to 80-100⁰C and maintaining the temperature for one hour. Separating the oil phase and the residue by filtration . (3) Grinding Bingpian, Sanqi and Ruxiang individually into very fine powders and passing the powders through a 180-mesh screen. Adding the powders into the hot oil phase and blending them thoroughly into a mixture .

(4) Adding melted Beeswax into the mixture in step (3) . Mixing them thoroughly.

(5) Cooling the final mixture to room temperature.

The final mixture looks purplish in color and is highly viscous .

Example 2 :

Materials used:

Bingpian: 2kg

Duyebaihi : 4kg

Huangbo : 4kg

Huangqin 4kg

MiIa: 16 kg

Ruxiang: 2kg

Vegetable oil: 100kg

Xujie: 2kg

Zicao: 4kg

Procedures of Preparation:

(1) Cutting Huangqin, Duyebaihi, Huangbo and Zicao into pieces. Soaking the mixed pieces in vegetable oil at room temperature for three days . (2) Heating the mixture of vegetable oil and the said pieces in step (1) up to 80-100⁰C and maintaining the temperature for one hour. Separating the oil phase and the residue by filtration .

(3) Grinding Bingpian, Ruxiang, and Xuejie into powder individually into very fine powders and passing the powders through a 180-mesh screen. Adding the powders into the oil phase obtained in step (2) and blending them thoroughly into a mixture .

(4) Adding melted MiIa into the mixture in step (3) . Mixing them thoroughly.

(5) Cooling the final mixture to room temperature.

In summary, this invention has provided a pharmaceutical composition which can be used at all stages of the healing process for open wounds. The composition can provide multiple medical effects that assist the entire healing process, including stop bleeding, pain relief, anti-inflammation, prevention and treatment of infection, and fostering of new soft tissue growth (including skin, subcutaneous tissue, fascia, fat, and muscle) . The compositions have potent antimicrobial qualities for a broad spectrum of wound pathogens including bacterial, virus, and fungus. The improved antimicrobial qualities can effectively prevent infection, control and quench local inflammation, promote microcirculation and reduce the efforts required to clean up the wound and/or replace the dressing by reducing the frequency of dressing changes. The compositions can last as long as three days before a clean-up and/or dressing change is needed. After being treated with these herbal compositions, the damaged tissue can quickly and naturally regenerate itself, which was previously considered impossible without skin grafting or transplant of fibroblast. The newly generated skin looks and functions more like normal skin, rarely leaving scars, keloids, or contracture after healing. This innovative treatment minimizes the need for plastic surgery.

This invention further provides a method for treating damaged skin comprising administering to the damaged skin a composition disclosed in this invention. Damaged skin includes traumatic wounds, burns (first, second and third degree), diabetic ulcers, pressure ulcers, stasis ulcers, decubitus ulcers, severe cuts, diaper rash, skin transplant sites, and abrasions. The invention proposes a single topical treatment for the damaged skin throughout the course of its healing. The pharmaceutical composition of the invention can be applied over the entire surface of the wound with a thickness of 1-2 mm (0.04-0.08 inch) . The wound area is covered with a gauze or second dressing. Then the gauze is secured in place with a tape or a secondary dressing. For deep wounds where packing is needed, it may be necessary to place cotton balls between the gauze pad and the securing tape to ensure the dressing is in complete contact with the surface of the wound. The dressing may be changed after one to three days. Stop using the pharmaceutical composition if no secretion is observed and the wound is enclosed and dry.

This invention also provides a pharmaceutical for the treatment of damaged skin comprising an effective amount of the composition and a pharmaceutically acceptable carrier. Examples of the pharmaceutically acceptable carrier include patches, gauze, film, membrane, dressing, bandage and other commonly used pharmaceutical carriers for treating damaged skin .

Case Study One:

The patient was a one-and-half years old girl who stick her both hands into a cooking pot containing boiling water. That caused 2nd degree burn to 95% area of her both hands. The burned areas appeared red with many blisters, and loss of skin in some areas . The wound was promptly treated with the pharmaceutical composition disclosed in Example 1. The pharmaceutical composition was reapplied topically every other day when the dressing was changed. After five days of treatment, burns were completely healed. The newly generated skin looked like normal skin, without trace of scars, contractures, keloids, or pigmentation changes. Fig. 2 shows the volar side of the burned hand before treatment. Fig. 3 shows the dorsal side of the burned hand before treatment. Fig. 4 and Fig. 5 show the volar side and the dorsal side of the baby's hand respectively one month after the treatment.

Case Study Two:

A male adult patient's both legs were severely burnt by boiling water. The boiling water caused large area of 2nd degree burning, approximately 70% of skin on both legs and feet. The pharmaceutical composition of the invention was applied over the entire surface of the wound with a thickness of 1-2 mm (0.04-0.08 inch) . The wound area was covered with gauze. Subsequently, the gauze was secured in place with a tape or a secondary dressing. The dressing was changed after three days. A thin film of newly generated skin tissue was observed at the first time of dressing change. Five days after, there was no further mucus secretions observed and the wound was enclosed and dry. The new skin tissue had grown back and the wound was healed in 15 days.

Case Study Three:

A 14-months-old girl pressed her right hand on a hot electric burner on a stove, leading to a 3rd degree burn on her index, middle, and ring fingers. The pharmaceutical composition of the invention was applied topically on the wound. The pain was instantly relieved. The wound was covered with gauze without further dressing change. No sign of infection was observed. The wound completely healed after 72 hours, leaving no scar or any other permanent damage. There are no pigments change observed. No appearance difference can be observed from the wound site.

DETAILED DESCRIPTION OF THE FIGURES

Fig. 1 displays a flow chart for preparing the ointment form of a pharmaceutical composition disclosed in this invention.

Fig. 2 shows the volar side of a one and half year-old baby's left hand. Fig. 3 shows the dorsal side. The pictures were taken before the treatment with the pharmaceutical composition .

Fig. 4 and Fig. 5 show the same hand one month after the treatment with the pharmaceutical composition. Fig. 4 shows the volar side and Fig. 5 shows the dorsal side, respectively. Compared to the Fig. 2 and Fig. 3, Figures 4 and 5 show the hand was fully healed without trace of scars, contractures, keloids, or pigmentation changes. The treatment period was five days .

Claims

CLAIMS What is claimed is :

1. A pharmaceutical comprising a composition which

comprises: (a) an anti-infection/antimicrobial composite, (b) a tissue regeneration composite, and optionally a pharmaceutically acceptable diluent or excipient; wherein the weight ratio of the anti-infection/antimicrobial composite versus the tissue regeneration composite is from approximately 3:1 to approximately 1:1.

2. A pharmaceutical according to claim 1, wherein said anti- infection/antimicrobial composite is selected from two or more of Bailian, Chuanxiong, Daihuang, Haiercha, Huangbo, Huanglian, Huangqin, Huzhang, Sijiqing, Zicao, and Zhizi.

3. A pharmaceutical according to claim 2, wherein said

tissue regeneration composite is selected from two or more of Bailian, Daihuang, Duyebaiji, Haiercha, Huzhang, Chuanxiong, Moyao, Ruxiang, Sanqi, Sijiqing, and Xuejie; wherein each of the selected anti-infection/antimicrobial herbal ingredient is different from any of the selected herbal ingredient in the tissue regeneration composite.

4. A pharmaceutical according to claim 3, wherein said

composition further comprises MiIa.

5. A pharmaceutical according to claim 3 or 4, wherein said composition further comprises Bingpian .

6. A pharmaceutical according to claim 3, wherein said anti- infection/antimicrobial composite contains at least Huanglian, Huzhang and Zicao.

7. A pharmaceutical according to claim 3 or 6, wherein said tissue regeneration composite contains at least Ruxiang and Sanqi .

8. A pharmaceutical according to claim 3, wherein said anti- infection/antimicrobial composite contains at least Huangqin, Huangbo and Zicao.

9. A pharmaceutical according to claim 3 or 8, wherein said tissue regeneration composition contains at least

Deyebaihi, Ruxiang and Xuejie.

10. A pharmaceutical according to claim 1, wherein the weight ratio of said anti-infection/antimicrobial composite versus the tissue regeneration composite is from approximately 2.5:1 to approximately 1.5:1.

11. A pharmaceutical according to claim 10, wherein said anti-infection/antimicrobial composite is selected from three or more of Bailian, Chuanxiong, Daihuang, Haiercha, Huangbo, Huanglian, Huangqin, Huzhang, Sijiqing, Zicao, and Zhizi.

12. A pharmaceutical according to claim 11, wherein said tissue regeneration composite is selected from two or more of Bailian, Daihuang, Duyebaiji, Haiercha, Huzhang, Chuanxiong, Moyao, Ruxiang, Sanqi, Sijiqing, and Xuejie; wherein each of the selected anti-infection/antimicrobial herbal ingredient is different from any of the selected herbal ingredient in the tissue regeneration composite.

13. A pharmaceutical according to claim 12, wherein said composition further comprises MiIa.

14. A pharmaceutical according to any of the claims 10 to 13; wherein said composition further comprises

Bingpian .

15. A pharmaceutical according to claim 12, wherein said anti-infection/antimicrobial composite contains at least Huanglian, Huzhang and Zicao.

16. A pharmaceutical according to claim 12 or 15,

wherein said tissue regeneration composite contains at least Ruxiang and Sanqi .

17. A pharmaceutical according to claim 12, wherein said anti-infection/antimicrobial composite contains at least Huangqin, Huangbo and Zicao.

18. A pharmaceutical according to claim 12 or 17,

wherein said tissue regeneration composition contains at least Deyebaihi, Ruxiang and Xuejie.

19. A pharmaceutical according to claim 1, wherein the anti-infection/antimicrobial composite comprising

Huanglian, Huzhang and Zicao, and the tissue regeneration composite comprising Ruxiang and Sanqi.

20. A pharmaceutical according to claim 19, wherein said composition further comprises Bingpian, and MiIa.

21. A pharmaceutical according to claim 1, wherein the anti-infection/antimicrobial composite comprising

Huangqin, Huangbo and Zicao; and the tissue regeneration composite comprising Duyebaihi, Ruxiang and Xuejie.

22. A pharmaceutical according to claim 21, wherein said composition further comprises Bingpian and MiIa.

23. A pharmaceutical according to any one of the claims 1- 22, wherein said composition further contains

vegetable oil .

24. A pharmaceutical according to any one of the claims 1-22, wherein said pharmaceutically acceptable diluent or excipient is vegetable oil, water, alcohol, or mixture of any of the above .

25. A pharmaceutical composition for the treatment of open wounds comprising an effective amount of the

composition of claim 1-24 and a pharmaceutically

acceptable carrier .

26. A method for the treatment of open wounds by

administrating to the subject an effective amount of the pharmaceutical composition of claims 1-24.

27. Use of a composition as defined in any one of claims 1 to 24 in the manufacture of a pharmaceutical to treat damaged soft tissue such as a wound or ulcer.

28. A process for preparing the pharmaceutical

composition described in claim 1, said process comprising the steps of: a) Cutting Zicao, Huzhang, Huanglian, into pieces and then soaking said pieces in vegetable oils for three days, b) Boiling the vegetable oil and said pieces up to 80- 100⁰C for one hour and maintaining the temperature for one hour, separating the oil phase and the residue by filtration,

c) Griding Bingpian, Sanqi and Ruxiang individually into powder so fine that they pass through a 180-mesh screen, adding the powders into the hot oil phase and blending them thoroughly into a mixture; and

d) Adding melted MiIa into the mixture in step (c) and mixing them thoroughly.

e) Cooling the final mixture to room temperature.

9. A process for preparing the pharmaceutical

composition described in claim 1, said process comprising the steps of: a) Cutting Huangqin Duyebaiji, Huangbo and Zicao into pieces and then soaking said pieces in vegetable oils for three days,

b) Boiling the vegetable oil and said pieces up to 80- 100⁰C for one hour and maintaining the temperature for one hour, separating the oil phase and the residue by filtration,

c) Griding Bingpian, Ruxiang and Xuejie individually into powder so fine that they pass through a 180-mesh screen, adding the powders into the hot oil phase and blending them thoroughly into a mixture; and

d) Adding melted MiIa into the mixture in step (c) and mixing them thoroughly.

e) Cooling the final mixture to room temperature.